Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care.

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title: Bladder Cancer in 2010: How Far have We Come?
abstract: Bladder cancer is the fourth most common cancer and ranks eighth as a cause of death from cancer among men in the United States. Although guidelines assist in treatment, the art of managing bladder cancer, such as the decision to use neoadjuvant chemotherapy and the timing of cystectomy, is still variable. Bladder cancer has a propensity to recur, and with recurrence, a significant number of cases progress, which makes the early detection of high‐risk patients imperative. Advances in detection, surveillance, and treatment of bladder cancer are reviewed in this article.

title: Bladder cancer staging
abstract: Bladder cancer is a common tumour of the urinary tract, accounting for 6±8% of all male malignancies and 2±3% of all female malignancies [1,2]. In south-eastern England, there were 3000 new registrations in 1992 and over 2000 deaths were reported in 1994 . Bladder cancer is generally considered a disease of later life, reaching a peak incidence in the sixth and seventh decades, although recent trends have revealed an increasing number of younger patients presenting with the disease . The epidemiology of bladder cancer shows strong associations with some environmental factors. An increased incidence of bladder cancer was noted in those working with aniline dyes over 100 years ago. Since then, aromatic amines have been shown to be associated with the development of bladder cancer, introducing an occupational hazard for workers involved with organic chemicals, rubber and paint materials. Diesel fumes and long-term use of the analgesic phenacetin have also been implicated in the development of the disease [4]. Cigarette smoking has an important association with urothelial cancer; cigarette smokers are two to six times more likely to develop the disease than those who do not smoke [5,6]. Cystitis and chronic urinary tract infection predispose to bladder cancer, and < 7% of bladder tumours occur within diverticula. Where schistosomiasis is endemic, there is a high incidence of epithelial tumours, mostly of squamous cell type [7,8]. There is a genetic predisposition to the development of bladder cancer . The clinical presentation of bladder cancer is classically with painless haematuria. Initial diagnostic manoeuvres do not involve imaging. Bacteriological and cytological examination of the urine frequently give signi®cant clues. Further investigation may be directed at the lower urinary tract, when cystoscopy is used. Imaging of the upper urinary tract involves a combination of crosssectional techniques and IVU. The vast majority of bladder tumours are epithelial in origin; of these < 90% are TCCs, the remainder being squamous cell carcinoma, adenocarcinoma and mixed tumours. A wide variety of nonepithelial tumours may affect the bladder. Leiomyosarcoma, rhabdomyosarcoma, phaeochromocytoma, hamartomatous malformations, lymphoma and metastases have been described. The imaging features of these rare tumours have been described only occasionally, but most present as a mass lesion which cannot be reliably discriminated from epithelial cancers using appearances on imaging alone. Of nonepithelial tumours, only lymphoma is suf®ciently common to be seriously considered in the differential diagnosis of a bladder wall mass. The other clinical circumstance which must be considered is that other pelvic tumours may invade directly into the bladder (e.g. carcinoma of the colorectal region, cervix and prostate). The imaging features of primary bladder tumours are essentially not speci®c; the diagnosis must always be con®rmed by cytology or histology, and imaging therefore plays a limited role at the time of diagnosis. Before computer-based cross-sectional imaging became available, mucosal lesions of the bladder could be detected with studies such as IVU, or cystography in which the bladder was ®lled with contrast medium, but the depth of invasion through the wall could not be assessed. With the advent of CT and ultrasonography (US) in the 1970s, and MRI in the 1980s, the penetration of epithelial tumours through the bladder wall can be depicted. Staging of tumours by imaging has become increasingly important in the management of bladder cancer as the available equipment has become more sophisticated. A variety of treatments now exist for bladder cancer and a rational choice is assisted by information from imaging studies. Accurate staging not only allows optimal treatment to be selected for the individual patient, but also allows valid comparisons to be made between different treatments given to patients with disease of similar stage. Some patients can still be staged by clinical means alone, but in most cases, some consideration should be given to the use of imaging as an adjunct.

title: Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.
abstract: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes.



All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients.



A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence.



These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

title: Clinical under staging of high risk nonmuscle invasive urothelial carcinoma treated with radical cystectomy.
abstract: The role of radical cystectomy in patients with nonmuscle invasive urothelial carcinoma of the bladder remains controversial. The risk of overtreatment must be balanced against the potential benefit of aggressive therapy. We reviewed our results in these patients with a particular emphasis on clinical under staging.



We reviewed the records of 214 consecutive patients who underwent radical cystectomy for urothelial carcinoma between April 1995 and August 1999, focusing on those with nonmuscle invasive, stages T1 or less disease. We assessed clinical and pathological data as well as outcomes based on pathological disease extent.



A total of 78 patients (36%) underwent radical cystectomy for clinical stages T1 or less disease. Indications included disease refractory to intravesical therapy in 29 cases (37%), pathological findings reflective of high grade stage T1 or multifocal disease in 26 (33%), radiographic suspicion of invasive disease in 15 (20%) and severe symptoms in 8 (10%). Cancer was clinically under staged with stages pT2 or greater disease in 31 patients (40%) according to final pathology results. Under staging was most pronounced in the 10 patients (67%) with suspicious radiography and in the 18 (64%) with absent muscle in the biopsy specimen. Of the 78 patients with pathological stages pT1 disease or less 98% had no evidence of disease compared to 65% with stages pT2 or greater disease (p <0.01).



Despite the intent to perform early cystectomy a significant percent of patients harbored occult muscle invasive and/or metastatic disease. In clinical and pathological, superficial stages T1 or less cases disease-free survival was excellent. Due to these results, the selection of high risk superficial transitional cell carcinoma cases for continued bladder sparing treatment should include uninvolved muscle on biopsy and absent radiographic suspicion of invasion.

title: Correlation between clinical and pathological staging in a series of radical cystectomies for bladder carcinoma
abstract: To analyse the rate of concordance between the clinical and pathological Tumour‐Nodes‐Metastasis staging systems in a homogeneous series of patients who had undergone radical cystectomy for locally advanced or recurrent multifocal superficial bladder carcinoma.

title: Urinary bladder cancer: diffusion-weighted MR imaging--accuracy for diagnosing T stage and estimating histologic grade.
abstract: To prospectively evaluate the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to be used to determine the T stage of bladder cancer and to measure the correlation between the apparent diffusion coefficient (ADC) and histologic grade.



This study was approved by the local institutional review board. All patients gave written informed consent. Forty patients with a total of 52 bladder tumors underwent MR imaging that included DW imaging. Histologic grade was determined for all tumors. Two radiologists interpreted four image sets (ie, T2-weighted images alone, T2-weighted plus DW images, T2-weighted plus dynamic contrast agent-enhanced images, all three image types together). Conventional criteria were used for interpreting T2-weighted and contrast-enhanced images. For DW images, new staging criterion developed on the basis of the hypothesis that tumors, submucosal tissue, and muscles show high, low, and intermediate signal intensity, respectively, was used. The McNemar test was used to examine differences in accuracy, sensitivity, and specificity. Differences in the performance were analyzed by comparing the areas under the receiver operating characteristic curves (A(z) values). To compare ADCs between three histologic grades, analysis of variance was used.



The overall accuracy of T stage diagnosis was 67% for T2-weighted images alone, 88% for T2-weighted plus DW images, 79% for T2-weighted plus contrast-enhanced images, and 92% for all three image types together. The overall accuracy, specificity, and A(z) for diagnosing T2 or higher stages were significantly improved by adding DW images (P < .01). The mean ADC of G3 tumors was significantly lower than that of G1 and G2 tumors (P < .01).



DW images provided useful information for evaluating the T stage of bladder cancer, particularly in differentiating T1 or lower tumors from T2 or higher tumors. The ADC may in part predict the histologic grade of bladder cancer.

title: Bladder tumour staging: comparison of diffusion- and T2-weighted MR imaging
abstract: The aim of this work was to evaluate the clinical feasibility of diffusion-weighted (DW) MRI in detection and staging of urinary bladder tumour and to compare DW MRI with the T2-weighted technique. One hundred and six patients with bladder tumour were prospectively included in our study. All patients were evaluated with MR imaging. We started with axial T2-weighted high resolution MR of the urinary bladder, then DW MRI. Two radiologists independently interpreted the MR images, and discrepancies were resolved by consensus. The accuracy of DW MRI in staging of bladder tumour was evaluated using the final histopathological findings. In DW imaging (DWI) staging accuracy was 63.6% and 69.6% in differentiating superficial from invasive tumours and organ-confined from non-organ-confined tumours, respectively. On a stage by a stage basis, DWI accuracy was 63.6% (21/33), 75.7% (25/33), 93.7% (30/32) and 87.5% (7/8) for stages T1, T2, T3 and T4, respectively. In the T2-weighted technique, the overall staging accuracy was only 39.6% and accuracy for differentiating superficial from invasive tumours and organ-confined from non-organ-confined tumours was 6.1% and 15.1%, respectively. DW is superior to T2-weighted MRI in staging of organ-confined tumours (≤T2) and both techniques are comparable in the evaluation of higher-stage tumours.

title: Genitourinary applications of diffusion-weighted MR imaging in the pelvis.
abstract: Diffusion-weighted (DW) magnetic resonance (MR) imaging has a large number of potential clinical applications in the female and male pelvis and can easily be added to any routine MR protocol. In the female pelvis, DW imaging allows improvement of staging in endometrial and cervical cancer, especially in locally advanced disease and in patients in whom contrast medium administration should be avoided. It can also be helpful in characterizing complex adnexal masses and in depicting recurrent tumor after treatment of various gynecologic malignancies. DW imaging shows promising results in monitoring treatment response in patients undergoing radiation therapy of cervical cancer. An increase in apparent diffusion coefficient (ADC) values of responders precedes changes in size and may therefore allow early assessment of treatment success. In the male pelvis, the detection of prostate cancer in the peripheral zone is relatively easier than in the central gland based on the underlying ADC values, whereas overlapping values reported in the central gland still need further research. DW imaging might also be applied in the noninvasive evaluation of bladder cancer to differentiate between superficial and muscle-invasive tumors. Initial promising results have been reported in differentiating benign from malignant pelvic lymph nodes based on the ADC values; however, larger-scale studies will be needed to allow the detection of lymph node metastases in an individual patient. Prerequisites for successfully performing DW imaging of the female and male pelvis are standardization of the DW imaging technique, including the choice of b values, administration of an antiperistaltic drug, and comparison of DW findings with those of morphologic MR imaging.

title: Bladder cancer: utility of MRI in detection of occult muscle-invasive disease
abstract: The presence of muscularis propria invasion by bladder cancer is a key factor in prognosis and treatment decisions, although may be missed by biopsy due to sampling error. MRI has shown potential for detection of muscle invasion but has not specifically been evaluated for this purpose in the setting of bladder cancer patients without evidence of muscle invasion on initial biopsy.  To evaluate the role of MRI in detection of muscularis propria invasion by bladder cancer following a pathologic diagnosis of non-invasive tumor.  This retrospective study included 23 patients who underwent pelvic MRI following a pathologic diagnosis of bladder cancer without muscularis propria invasion and in whom additional histologic evaluation was performed following MRI. Two radiologists in consensus reviewed T2-weighted images to identify those cases suspicious for muscle invasion on MRI. The radiologists identified whether cases suspicious for invasion demonstrated disruption of the T2-hypointense muscularis layer of the bladder wall, peri-vesical fat stranding, and peri-vesical soft tissue nodularity. Findings were compared with pathologic results obtained after MRI.  Suspicion was raised for muscle invasion in eight of 23 cases, four of which exhibited invasion on follow-up pathology. No case without suspicion on MRI exhibited invasion on follow-up pathology. Therefore, sensitivity and specificity were 100% and 79%, respectively. Among individual findings, muscularis disruption on T2WI exhibited sensitivity of 100% and specificity of 79%, peri-vesical fat stranding exhibited sensitivity and specificity of 50% and 84%, and peri-vesical soft tissue nodularity exhibited sensitivity and specificity of 25% and 100%.  MRI demonstrated high sensitivity for detection of muscle invasion in cases of bladder cancer without invasion on initial histologic assessment. Muscularis disruption on T2WI appeared to exhibit a better combination of sensitivity and specificity than did peri-vesical changes.

title: The value of diffusion-weighted MRI in the diagnosis of malignant and benign urinary bladder lesions.
abstract: To investigate the role of diffusion-weighted MRI (DWI) in the diagnosis of urinary bladder (UB) tumours by means of measuring apparent diffusion coefficient (ADC) values.



A total of 83 people aged between 18 and 86 years were included in the study: 63 patients with UB pathology (46 malignant, 17 benign) constituted the case group; 20 individuals without any UB pathology constituted the control group. DWI was applied to all individuals. The ADC values were measured based on the tissue of the UB mass entities and normal UB wall in the control group.



The mean ADC value in the UB carcinoma group was significantly lower than that in the control group: 1.0684 ± 0.26 × 10(-3) mm(2) s(-1) and 2.010 ± 0.11 × 10(-3) mm(2) s(-1), respectively (p<0.01). There was a significant difference among the mean ADC values of different grades of malignant tumours, corresponding to 0.9185 ± 0.20 mm(2) s(-1) and 1.281 ± 0.18 mm(2) s(-1) in high-grade and low-grade malignant UB carcinomas, respectively (p<0.01). The ADC value in the carcinoma group was significantly lower than that in the benign lesion group: 1.0684 ± 0.26 × 10(-3) mm(2) s(-1) and 1.803 ± 0.19 × 10(-3) mm(2) s(-1), respectively (p<0.01). All 46 malignant lesions displayed a restriction in diffusion; 4 of the 17 benign lesions displayed a mild restriction in diffusion. The sensitivity, specificity and accuracy of DWI in the diagnosis of malignant UB lesions was 100%, 76.5% and 93.65%, respectively.



DWI can be beneficial in the differentiation of benign and malignant UB lesions, as well as of high-grade and low-grade UB carcinomas, using quantitative ADC measurements.

title: Apparent diffusion coefficient value reflects invasive and proliferative potential of bladder cancer
abstract: To elucidate a role of apparent diffusion coefficient (ADC) value as a biomarker of bladder cancer, we investigated its associations with Ki‐67 labeling index (LI) along with classical clinicopathological prognosticators.

title: Quantitative Apparent Diffusion Coefficient Measurements Obtained by 3-Tesla MRI Are Correlated with Biomarkers of Bladder Cancer Proliferative Activity
abstract: To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.  Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.  Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).  ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.

title: Whole-lesion diffusion metrics for assessment of bladder cancer aggressiveness
abstract: PurposeTo explore associations of whole-lesion histogram diffusion metrics with pathologic findings and subsequent metastatic disease in bladder cancer patients undergoing radical cystectomy.MethodsTwenty-three bladder cancer patients (21M, 2F; mean 70 ± 11 years) underwent MRI before cystectomy. A volume-of-interest was placed on all slices on the ADC map encompassing each lesion. Whole-lesion mean, kurtosis, and skewness of ADC were calculated and compared with T stage and pelvic nodal status at cystectomy and with subsequent metastasis in 20/25 patients with available follow-up.ResultsAt cystectomy, 39 % (9/23) were stage T2, 61 % (14/23) ≥T3, and 28 % (5/23) exhibited positive nodes; 35 % (7/20) developed later metastases. Mean ADC was significantly lower in stage ≥T3 than in lower stage tumors (1.20 ± 0.36 × 10−3 vs. 1.55 ± 0.36 × 10−3 mm2/s; p = 0.044), but showed no association with nodal or metastatic disease (p = 0.362–0.709). Kurtosis was significantly lower in tumors with, compared to without, nodal disease (−0.05 ± 0.29 vs. 0.91 ± 1.16; p = 0.037), and showed a non-significant decrease in tumors with, compared to without, later metastases (0.23 ± 0.63 vs. 0.83 ± 0.89; p = 0.088). Kurtosis was not associated with T stage (p = 0.811), and skew was not associated with any outcome (p = 0.516–0.643). Mean ADC achieved highest AUC for identification of stage ≥T3 (AUC = 0.754 vs. 0.516–0.643 for other metrics). Kurtosis achieved highest AUC for nodal disease (AUC = 0.811 vs. 0.522–0.556 for other metrics) and metastases (AUC = 0.736 vs. 0.516–0.626 for other metrics). Only difference in AUC between skewness and kurtosis for nodal disease was significant (p = 0.031).ConclusionWhile requiring larger studies, kurtosis has potential to complement mean ADC in bladder cancer prognosis using whole-lesion histogram analysis.

title: Prospective evaluation of diffusion-weighted MRI of the bladder as a biomarker for prediction of bladder cancer aggressiveness.
abstract: To prospectively test the utility of diffusion-weighted magnetic resonance imaging (DW-MRI) for bladder cancer (BCA) staging and grading.



We prospectively enrolled 51 consecutive patients (median age = 64 y, range: 30-90y) with suspected BCA with or without gross hematuria who received 3-T DW-MRI before transurethral resection of the bladder. Parametric apparent diffusion coefficient (ADC) maps were automatically calculated from DW-MRI. ADC values (given in × 10(-3)mm(2)/s) of bladder lesions were independently measured by 2 radiologists blinded to histopathology. Comparisons of ADC values with histopathologic features were performed using unpaired t tests. Diagnostic performance was calculated by means of receiver operating characteristics (ROC) statistics.



We excluded 8 patients: 1 presenting with metastatic melanoma to the bladder, 1 who had an incomplete examination, and 6 without BCA. In the 43 remaining patients (median age = 68 y, range: 41-85 y), the ADC values were lower in high-grade (n = 19, ADC = 0.787) compared with low-grade (n = 24, ADC = 1.233) tumors (P<0.0001) and in muscle-invasive tumors (n = 10, ADC = 0.759) compared with non-muscle-invasive tumors (n = 33, ADC = 1.120, P = 0.0004). The area under the ROC curve was 0.884 for prediction of muscle invasion and 0.906 for prediction of high grade by using ADC values. Rule-in ADC criteria for high-grade lesions and rule-out ADC criteria for muscle invasion were identified by ROC analysis.



ADC measurements obtained by DW-MRI are a promising imaging biomarker for prediction of BCA stage and grade providing high sensitivity and specificity. Further studies are necessary to establish the value of this test in guiding decision making in clinical practice.

title: MR imaging of urinary bladder cancer for T‐staging: A review and a pictorial essay of diffusion‐weighted imaging
abstract: Treatment decisions for bladder cancer patients are mainly based on the depth of bladder wall invasion by the tumor. In this article, we review the conventional MRI and exhibit a recently emerged diffusion‐weighted imaging (DWI) of urinary bladder cancer for T‐staging. We discuss limitations of conventional MRI, scanning protocols of DWI, normal pelvic findings on DWI, determination of T‐stage using DWI, and pitfalls of DWI. DWI provides high contrast between bladder cancer and background tissue because the cancer shows markedly high SI. DWI has high sensitivity for detecting the stalk seen in stage Ta or T1. An inflammatory change or fibrosis surrounding the tumor mimics the invasion of bladder cancer on T2‐weighted imaging or enhanced MRI and could lead to over‐staging, but DWI could differentiate them clearly because these benign changes do not show high SI on DWI. DWI is also useful for detecting ureteral, urethral, and prostatic extension by means of the urethra. DWI provides more accurate information on the extent of bladder cancer and contributes to determination of the treatment strategy.  Imaging 2013;38:1299–1309.

title: Role of diffusion‐weighted magnetic resonance imaging as an imaging biomarker of urothelial carcinoma
abstract: Diffusion‐weighted magnetic resonance imaging is a type of functional imaging that is increasingly being applied in the management of upper tract urothelial carcinoma and bladder cancer. The image contrast is derived from differences in the Brownian motion of water molecules in tissues. The homogenous high signal intensity of upper tract urothelial carcinoma and bladder cancer on diffusion‐weighted magnetic resonance imaging provides helpful diagnostic information for the presence of cancerous lesions in a non‐invasive manner. Recently, growing evidence has emerged showing that diffusion‐weighted magnetic resonance imaging can serve as an imaging biomarker for characterizing cancer pathophysiology, because the signal reflects biophysical information about the tissues. Quantitative analysis by evaluating the apparent diffusion coefficient values potentially reflects the histological grade and the biological aggressiveness of urothelial carcinoma. The apparent diffusion coefficient value could be a biomarker predicting the clinical course of upper tract urothelial carcinoma and bladder cancer. In addition, in chemoradiotherapy‐based bladder‐sparing approaches against muscle‐invasive bladder cancer, the role of diffusion‐weighted magnetic resonance imaging for predicting the chemoradiosensitivity and for monitoring therapeutic response has been shown. Diffusion‐weighted magnetic resonance imaging is expected to improve the diagnostic accuracy, and this qualitative information might allow individualized treatment strategies for patients with urothelial carcinoma.

title: Diffusion-weighted magnetic resonance imaging in management of bladder cancer, particularly with multimodal bladder-sparing strategy.
abstract: Bladder-sparing strategy for muscle-invasive bladder cancer (MIBC) is increasingly demanded instead of radical cystectomy plus urinary diversion. Multimodal therapeutic approaches consisting of transurethral resection, chemotherapy, radiotherapy and/or partial cystectomy improve patients' quality of life by preserving their native bladder and sexual function without compromising oncological outcomes. Because a favorable response to chemoradiotherapy (CRT) is a prerequisite for successful bladder preservation, predicting and monitoring therapeutic response is an essential part of this approach. Diffusion-weighted magnetic resonance imaging (DW-MRI) is a functional imaging technique increasingly applied to various types of cancers. Contrast in this imaging technique derives from differences in the motion of water molecules among tissues and this information is useful in assessing the biological behavior of cancers. Promising results in predicting and monitoring the response to CRT have been reported in several types of cancers. Recently, growing evidence has emerged showing that DW-MRI can serve as an imaging biomarker in the management of bladder cancer. The qualitative analysis of DW-MRI can be applied to detecting cancerous lesion and monitoring the response to CRT. Furthermore, the potential role of quantitative analysis by evaluating apparent diffusion coefficient values has been shown in characterizing bladder cancer for biological aggressiveness and sensitivity to CRT. DW-MRI is a potentially useful tool for the management of bladder cancer, particularly in multimodal bladder-sparing approaches for MIBC.

title: Diffusion-weighted MRI in the body: applications and challenges in oncology.
abstract: In this article, we present the basic principles of diffusion-weighted imaging (DWI) that can aid radiologists in the qualitative and quantitative interpretation of DW images. However, a detailed discussion of the physics of DWI is beyond the scope of this article. A short discussion ensues on the technical aspects of performing DWI in the body. The emerging applications of DWI for tumor detection, tumor characterization, distinguishing tumor tissue from nontumor tissue, and monitoring and predicting treatment response are highlighted. The challenges to widespread adoption of the technique for cancer imaging in the body are discussed.



DWI derives its image contrast from differences in the motion of water molecules between tissues. Such imaging can be performed quickly without the need for the administration of exogenous contrast medium. The technique yields qualitative and quantitative information that reflects changes at a cellular level and provides unique insights about tumor cellularity and the integrity of cell membranes. Recent advances enable the technique to be widely applied for tumor evaluation in the abdomen and pelvis and have led to the development of whole-body DWI.

title: The diagnostic value of diffusion-weighted magnetic resonance imaging in soft tissue abscesses.
abstract: To study the diagnostic value of diffusion-weighted imaging (DWI) in soft tissue abscesses.



Fifty patients were included in this study who were thought to have soft tissue abscess or cystic lesion as a result of clinical and radiological examinations. Localisations of the lesions were: 1 periorbital, 3 breast, 14 intraabdominal, and 32 intramuscular lesions. After other radiological examinations, DWI was performed. The signal intensity values of the lesions were evaluated qualitatively according to the hyperintensity on b-1000 DWI, using 1.5 T MR system. All of the lesions were aspirated after DWI, and detection of pus in the aspiration material was accepted as gold standard for the diagnosis of abscess.



In 38 of the 50 patients, hyperintensity was obtained on diffusion-weighted images. False-positive results were maintained in 2 of these patients, and true-positive results were maintained in 36 of them. In 11 of the 50 patients, hypointensity was visualised on diffusion-weighted images. False-negative results were maintained in 3 of these patients, and true-negative results were maintained in 8 of them. An abscess which was seen on post-contrast conventional MRI could not be seen on DWI, and this was regarded as false-negative.



The sensitivity and specificity of diffusion-weighted images for detecting soft tissue abscesses were found to be 92% and 80%, respectively. DWI has a high diagnostic value in soft tissue abscesses, and is an important imaging modality that may be used for the differentiation of cysts and abscesses.

title: Diffusion-weighted MR imaging for urinary bladder carcinoma: initial results
abstract: The aim of this study was to demonstrate the feasibility of using diffusion-weighted (DW) magnetic resonance (MR) imaging under free breathing for the detection of a urinary bladder carcinoma. In 15 patients with 17 urinary bladder carcinomas, DW images were obtained in the axial plane under free breathing scanning with a multisection spin-echo type single-shot echo planar sequence with a body coil. DW images were evaluated based on cystoscopic findings. Moreover, the apparent diffusion coefficient (ADC) value was measured in a circular region of interest (ROI) within the carcinoma, urine, normal bladder wall, prostate and seminal vesicle. In the results, on the DW images, all 17 carcinomas were clearly shown as high signal intensity relative to the surrounding structure. The ADC value (×10−3 mm2/s) in the carcinoma was 1.18±0.19, which was significantly lower compared with that of urine (3.28±0.20), the normal bladder wall (2.27±0.24), prostate (transition zone: 1.57±0.09, peripheral zone:1.85±0.22) and seminal vesicle (2.01±0.22). In conclusion, DW images under free breathing enabled the clear detection of the urinary bladder carcinoma, whose ADC values were lower compared with those of the surrounding structure. The DW images may be useful in evaluating tumors invading to the surrounding structures.

title: Role of Diffusion MRI and Apparent Diffusion Coefficient Measurement in the Diagnosis, Staging and Pathological Classification of Bladder Tumors
abstract: Our aim was to investigate the role of simultaneous apparent diffusion coefficient (ADC) measurement and diffusion-weighted MRI (DWMRI) in the diagnosis and differentiation of bladder masses.  Weexamined 45 patients presenting with hematuria by dynamic and diffusion MRI (at b100, b600, b1000 gradients) and cystoscopy. Thirty healthy volunteers without hematuria were also included in the study. Results from imaging techniques were compared to cystoscopic and histopathologic findings. The ADC values of benign and malignant bladder masses, and bladder tissue in healthy subjects were measured and compared with each other.  The mean ADC values of benign (n = 10) and malignant lesions (n = 35) were significantly lower than the mean ADC values of adjacent bladder walls and bladder walls of healthy subjects at all 3 gradients (p < 0.05). However, no significant difference was detected between benign and malignant lesions (p > 0.05). Mean ADC values of invasive tumors were significantly lower than superficial malignancies at b600 and b1000 gradients. The mean ADC values of transitional cell tumors were significantly higher than squamous cell tumors at b100 and b600 gradients.  Simultaneous measurement ofADC and DWMRI provided useful information in the diagnosis, staging and histopathological classification of bladder tumors.

title: Agreement and Reproducibility of Apparent Diffusion Coefficient Measurements of Dual-b-Value and Multi-b-Value Diffusion-Weighted Magnetic Resonance Imaging at 1.5 Tesla in Phantom and in Soft Tissues of the Abdomen
abstract: To compare the coefficient of variation (CV) and long-term reproducibility of apparent diffusion coefficient (ADC) in a simple fluid-filled phantom and abdominal organs simultaneously.  Retrospective institutional review board–approved and Health Insurance Portability and Accountability Act–compliant study sequentially selected 100 patients who underwent clinically indicated abdominal magnetic resonance imaging. A subset of 58 patients had repeat scans within 2 to 5 months after the initial magnetic resonance imaging. Two diffusion-weighted imaging techniques (b-values 0–750 mm2/s) were performed to compare the ADC values. Mean ADC values were calculated for 10 locations and the reference phantom. The CV and Bland-Altman plots were calculated for the phantom and soft tissues at each session and location.  There were no significant differences in the mean ADC values between repeated acquisitions. However, ADC values were statistically higher using dual-b-value than multi-b-value diffusion-weighted imaging. The CV for the phantom was 8.6 versus 10.8 for dual-b-value and multi-b-value, respectively. The CVs for the soft tissues had a wider range compared with that of the phantom (liver, 12.6 vs 9.0; spleen, 11.7 vs 11.2; gallbladder, 11.0 vs 13.6; head of pancreas, 14.6 vs 14.7; body of pancreas, 13.4 vs 13.0; tail of pancreas, 14.8 vs 16.3; right kidney, 9.1 vs 9.6; left kidney, 9.3 vs 9.3; right paraspinal muscle, 7.9 vs 7.5; left paraspinal muscle, 7.3 vs 7.3, respectively).  A change in ADC less than 11% falls into the range of measurement variability. Paraspinal muscle could potentially be used as an internal reference parameter.

title: Diffusion-weighted MRI of urinary bladder and prostate cancers.
abstract: The purpose of this study was to evaluate the feasibility of diffusion-weighted imaging in the diagnosis of the urinary bladder and prostate carcinomas. The apparent diffusion coefficient (ADC) values of the malignant and normal tissues were correlated.



A total of 23 patients with 14 urinary bladder carcinomas and 9 prostate carcinomas, and 50 healthy controls with normal ultrasonographic urinary bladder and prostate gland imaging findings were enrolled in the study. The ADC values were reported as the mean +/- standard deviation. Student's t test was performed to compare the ADC values of the normal and pathological tissues. Diffusion-weighted imaging (DWI) was performed with b factors of 0, 500, and 1000 s/mm(2), and the ADC values of the normal tissues and lesions were calculated.



The mean ADC value of the urinary bladder wall of the control group and bladder carcinomas were (2.08 +/- 0.22 x 10(-3)mm(2)/s) and (0.94 +/- 0.18 x 10(-3)mm(2)/s), respectively. In addition, the ADC values of the normal peripheral (2.07 +/- 0.33 x 10(-3)mm(2)/s), transitional zones (1.46 +/- 0.23 x 10(-3)mm(2)/s) of the prostate, seminal vesicles (2.13 +/- 0.13 x 10(-3)mm(2)/s) and the prostate carcinomas (1.06 +/- 0.17 x 10(-3)mm(2)/s) were calculated. The comparison of mean ADC values of the peripheral-transitional zones of the prostate, normal bladder wall-bladder carcinomas, and peripheral zone prostate carcinomas were statistically significant (P < 0.01).



The present study demonstrated that ADC measurement has a potential ability to differentiate carcinomas from normal bladder wall and prostate gland.

title: Utility of diffusion-weighted MRI in the diagnosis of bladder carcinoma.
abstract: The purposes of our study were to investigate the feasibility of diffusion-weighted imaging in the detection of malignant bladder tumors, with comparison to the high-resolution thin-section fast spin-echo (FSE) T2-weighted MRI, and also to compare the apparent diffusion coefficient (ADC) values of the bladder tumors with the surrounding structures.



Fifty-three consecutive patients consisting of 44 males and 9 females who presented with a bladder mass were prospectively enrolled in this study. Mean age was 62.53 ± 12.03 (age range, 33-86 years). These patients were evaluated by high-resolution thin-section FSE T2-weighted and diffusion-weighted MRI for the detection of bladder masses. Following MRI, within 2 weeks, all patients were subjected to either surgery or cystoscopic biopsy, and the obtained histopathological proofs were used as the reference standard. Furthermore, ADC values of the bladder tumors, urine, the normal bladder wall, the central and peripheral zones of the prostate, the seminal vesicule, and the uterus outer myometrium were also calculated. ADC values of the bladder carcinomas and the related surrounding structures were compared as to whether a statistically significant difference was present or not.



In a total of 47 patients, consisting of 39 males and 8 females, bladder carcinomas were clearly shown as having conspicuous high and intermediate signal intensity masses, relative to the surrounding structures on diffusion-weighted and T2-weighted images, respectively. An 89% sensitivity and a 100% positive predictive value were obtained for both FSE T2-weighted and diffusion-weighted MRI in the diagnosis of bladder carcinoma. Mean ADC values and standard deviations of the bladder tumors and the surrounding structures were as follows: bladder carcinomas (n=47): 1.28 ± 0.31, normal bladder wall (n=47): 1.98 ± 0.41, urine (n=47): 3.12 ± 0.24, seminal vesicle (n=39): 1.82 ± 0.33, peripheral zone of prostate (n=39): 1.80 ± 0.29, central zone of prostate (n=39): 1.55 ± 0.33, and uterus outer myometrium (n=8): 1.53 ± 0.19. It can be clearly seen that the mean ADC values of the bladder carcinomas were significantly lower than the surrounding structures (P<.05).



High-resolution thin-section FSE T2 and diffusion-weighted MRI show high diagnostic performance and are comparable in the detection of bladder tumors. Diffusion-weighted MRI provides high quality images of the malignant bladder tumors against a suppressed background signal. Diffusion-weighted MRI using ADC measurements may be useful in the evaluation of tumor invasion to the adjacent organs.

title: Histogram analysis of apparent diffusion coefficient at 3.0 T in urinary bladder lesions: correlation with pathologic findings.
abstract: To investigate the potential value of histogram analysis of apparent diffusion coefficient (ADC) obtained at standard (700 s/mm(2)) and high (1500 s/mm(2)) b values on a 3.0-T scanner in the differentiation of bladder cancer from benign lesions and in assessing bladder tumors of different pathologic T stages and to evaluate the diagnostic performance of ADC-based histogram parameters.



In all, 52 patients with bladder lesions, including benign lesions (n = 7) and malignant tumors (n = 45; T1 stage or less, 23; T2 stage, 7; T3 stage, 8; and T4 stage, 7), were retrospectively evaluated. Magnetic resonance examination at 3.0 T and diffusion-weighted imaging were performed. ADC maps were obtained at two b values (b = 700 and 1500 s/mm(2); ie, ADC-700 and ADC-1500). Parameters of histogram analysis included mean, kurtosis, skewness, and entropy. The correlations between these parameters and pathologic results were revealed. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic value of histogram parameters.



Significant differences were found in mean ADC-700, mean ADC-1500, skewness ADC-1500, and kurtosis ADC-1500 between bladder cancer and benign lesions (P = .002-.032). There were also significant differences in mean ADC-700, mean ADC-1500, and kurtosis ADC-1500 among bladder tumors of different pathologic T stages (P = .000-.046). No significant differences were observed in other parameters. Mean ADC-1500 and kurtosis ADC-1500 were significantly correlated with T stage, respectively (ρ = -0.614, P < .001; ρ = 0.374, P = .011). ROC analysis showed that the combination of mean ADC-1500 and kurtosis ADC-1500 has the maximal area under the ROC curve (AUC, 0.894; P < .001) in the differentiation of benign lesions and malignant tumors, with a sensitivity of 77.78% and specificity of 100%. AUCs for differentiating low- and high-stage tumors were 0.840 for mean ADC-1500 (P < .001) and 0.696 for kurtosis ADC-1500 (P = .015).



Histogram analysis of ADC-1500 at 3.0 T can be useful in evaluation of bladder lesions. A combination of mean ADC-1500 and kurtosis ADC-1500 may be more beneficial in the differentiation of benign and malignant lesions. Mean ADC-1500 was the most promising parameter for differentiating low- from high-stage bladder cancer.

title: Diffusion-weighted MRI in prostate cancer -- comparison between single-shot fast spin echo and echo planar imaging sequences.
abstract: Diffusion-weighted (DW) MRI at 1.5 T was carried out in two groups of patients. MRI data were correlated with the biopsy and histopathology (where available). The performance of two sequences -- a single-shot FSE (14 patients) and a single-shot EPI (15 patients) -- was compared. Average ADC values from the normal peripheral zone (PZ), central gland (CG) and the tumour [prostate carcinoma (PCa)] were calculated from b values of 0 and 600. Tukey-Kramer test was used for statistical analysis. EPI produced higher values of ADC (10(-3) mm(2)/s) than FSE sequence: 1.992+/-0.208 vs. 1.573+/-0.270 in PZ (P<.001), 1.518+/-0.126 vs. 1.373+/-0.179 in CG and 1.214+/-0.254 vs. 0.993+/-0.158 in PCa (P<.01). In conclusion, both EPI and FSE sequences showed differences in ADC between normal PZ, CG and PCa; however, EPI produced significantly higher ADC values than FSE.

title: Diffusion coefficient measurement using a temperature‐controlled fluid for quality control in multicenter studies
abstract: To present the use of a quality control ice‐water phantom for diffusion‐weighted magnetic resonance imaging (DW‐MRI). DW‐MRI has emerged as an important cancer imaging biomarker candidate for diagnosis and early treatment response assessment. Validating imaging biomarkers through multicenter trials requires calibration and performance testing across sites.

title: Short- and midterm reproducibility of apparent diffusion coefficient measurements at 3.0-T diffusion-weighted imaging of the abdomen.
abstract: To test the hypothesis that there is no significant variability in apparent diffusion coefficients (ADCs) at assessment of the short- and midterm reproducibility of ADC measurements in a healthy population.



Twenty healthy male volunteers were enrolled in this prospective institutional review board-approved study after they provided written informed consent. A 3.0-T magnetic resonance (MR) system was used to perform five axial diffusion-weighted (DW) abdominal acquisitions (session 1). A mean of 147 days +/- 20 (standard deviation) later, 16 of the 20 volunteers were imaged again with use of the same protocol and MR system (session 2). The mean ADCs for three regions of interest (ROIs) in five anatomic locations (right hepatic lobe, spleen, and head, body, and tail of pancreas) were calculated. The coefficient of variation (CV, equal to standard deviation divided by mean) was calculated for each subject, session, and anatomic location. The ADC and CV data were then analyzed by using repeated-measures analysis of variance.



There were significant differences (P < .001) in mean ADCs among the five anatomic locations. There were no significant differences in ADCs among the various repeated sequence acquisitions or the three ROIs. There were no significant differences in ADCs between imaging sessions 1 and 2. ADCs were fairly stable over the midterm within a given individual. Finally, there were no significant differences in resulting CVs between the imaging sessions or anatomic locations. The mean CV for ADC measurement reproducibility was 14% (95% confidence interval: 13%, 15%).



The mean CV for short- and midterm ADC reproducibility was 14% at abdominal DW imaging. Treatment effects of less than approximately 27% (change in ADC divided by pretreatment ADC) will not be clinically detectable with confidence with one acquisition in a single individual.

title: Diffusion-Weighted Imaging With Apparent Diffusion Coefficient Mapping and Spectroscopy in Prostate Cancer
abstract: Prostate cancer is a major health problem, and the exploration of noninvasive imaging methods that have the potential to improve specificity while maintaining high sensitivity is still critically needed. Tissue changes induced by tumor growth can be visualized by magnetic resonance imaging (MRI) methods. Current MRI methods include conventional T2-weighted imaging, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping and magnetic resonance spectroscopy (MRS). Techniques such as DWI/ADC provide functional information about the behavior of water molecules in tissue; MRS can provide biochemical information about the presence or absence of certain metabolites, such as choline, creatine, and citrate. Finally, vascular parameters can be investigated using dynamic contrast-enhanced MRI. Moreover, with whole-body MRI and DWI, metastatic disease can be evaluated in 1 session and may provide a way to monitor treatment. Therefore, when combining these various methods, a multiparametric data set can be built to assist in the detection, localization, assessment of prostate cancer aggressiveness, and tumor staging. Such a comprehensive approach offers more power to evaluate prostate disease than any single measure alone. In this article, we focus on the role of DWI/ADC and MRS in the detection and characterization using both in vivo and ex vivo imaging of prostate pathology.

title: Age‐related and zonal anatomical changes of apparent diffusion coefficient values in normal human prostatic tissues
abstract: To identify age‐related changes and differences in the diffusion of water molecules within the prostate, through diffusion‐weighted imaging (DWI) of the prostate gland in healthy adult Japanese men.

title: Value of normalized apparent diffusion coefficient for estimating histological grade of vesical urothelial carcinoma.
abstract: To compare the efficacy of apparent diffusion coefficient (ADC) and normalized ADC (nADC) for estimating the histological grade of vesical urothelial carcinoma and to identify an optimal reference for nADC calculation.



Thirty patients with histologically confirmed vesical urothelial carcinomas underwent preoperative diffusion-weighted magnetic resonance imaging (DW-MRI) of the pelvis. nADC of the tumour was calculated as ADC (tumour)/ADC (reference) using urine in the bladder lumen, and the obturator internus and gluteus maximus muscles as reference. Receiver operating characteristic (ROC) curves were constructed and compared to identify an optimal reference for nADC calculation.



Both ADC and nADC of low-grade tumours (1.112 ± 0.159 × 10(-3) mm(2)/s, 0.403 ± 0.047 × 10(-3) mm(2)/s) were significantly (p < 0.001) higher than those of high-grade tumours (0.772 ± 0.091 × 10(-3) mm(2)/s, 0.276 ± 0.033 × 10(-3) mm(2)/s). The area under the nADC ROC curve using urine as reference was significantly (p = 0.000) larger (0.995) than those using obturator internus (0.960) and gluteus maximus (0.945).



nADC is superior to ADC for estimating the histological grade of bladder carcinoma using urine in the bladder lumen as an optimal reference for nADC calculation.

title: Conventional and diffusion-weighted MRI features in diagnosis of metastatic lymphadenopathy in bladder cancer.
abstract: To compare qualitative and quantitative imaging features from conventional and diffusion-weighted (DW) magnetic resonance imaging (MRI) in detection of metastatic pelvic lymph nodes in bladder cancer patients undergoing cystectomy.



Thirty-six patients who had undergone cystectomy for bladder cancer with preoperative MRI with DWI sequence prior to surgery were included. Imaging features on conventional and DW-MRI were compared with histopathology at cystectomy.



Nodal features associated with metastatic lymphadenopathy were short axis (AUC = 0.85, p < 0.001; when SA > 5 mm: sensitivity = 88%, specificity = 75%), long axis (AUC = 0.80, p < 0.001; when LA > 6 mm: sensitivity = 88%, specificity = 71%), apparent diffusion coefficient (ADC) on DWI, normalized to muscle (AUC = 0.66, p = 0.113; when nADC < 1.35: sensitivity = 75%, specificity = 68%), and absence of fatty hilum on conventional imaging (AUC = 0.73, p = 0.012; when fatty hilum absent, sensitivity = 75%, specificity = 71%). ADC without normalization was not associated with metastasis (p = 0.303).



Imaging findings from conventional MRI and DWI achieved reasonable accuracy for detecting metastatic lymph nodes in bladder cancer, although sensitivity was higher than specificity. A short axis greater than 5 mm on conventional MRI had the highest accuracy of any individual finding. When using DWI, normalization of ADC values to muscle ADC may improve diagnostic performance.

title: Bladder cancer: diagnosis with diffusion-weighted MR imaging in patients with gross hematuria.
abstract: To prospectively evaluate the usefulness of diffusion-weighted (DW) magnetic resonance (MR) imaging for the detection of bladder neoplasms in patients with gross hematuria of lower urinary tract origin.



The study protocol received institutional ethical committee approval, and informed consent was obtained. Between April 2007 and March 2008, 130 consecutive patients with gross hematuria whose upper urinary tract had a normal appearance at ultrasonographic examination were prospectively enrolled. Mean age was 59.4 years (range, 45-75 years). All patients were evaluated by using T2-weighted high-spatial-resolution MR imaging of the urinary bladder, followed by DW MR imaging. Two radiologists independently interpreted the T2-weighted and DW images, and discrepancies were resolved by consensus. Agreement was evaluated by using the kappa statistic. All patients underwent conventional cystoscopy. With cystoscopy and the final histopathologic findings as the reference standards, a comparison with imaging findings was performed by using the McNemar test.



The consensus diagnostic performance of DW MR imaging for identification of bladder tumors was: sensitivity, 98.1% (104 of 106); specificity, 92.3% (24 of 26); PPV, 100% (104 of 104); negative predictive value, 92.3% (24 of 26); and accuracy, 97.0% (128 of 132). Two cases were falsely negative on T2-weighted MR images but were correctly diagnosed by using DW MR images. The agreement between DW MR imaging results and cystoscopic findings was excellent (kappa = 0.94) for identification of bladder neoplasm. DW MR imaging had a sensitivity and PPV of 98.5% (128 of 130) and 100% (128 of 128), respectively, for determining the cause of hematuria.



DW MR imaging is a highly reliable imaging approach for identification of bladder tumors in patients with gross hematuria.

title: Abdominal MRI at 3.0 T: the basics revisited.
abstract: The purpose of our article is to describe the underlying physics concepts of abdominal MRI at 3.0 T and their impact on signal-to-noise ratio, susceptibility artifacts, chemical shift artifacts, and dielectric effects.



Abdominal MR sequence protocols optimized for 1.5-T scanners should not be transferred to 3.0 T without substantial modification. In addition, specific patient groups--for example, large patients with ascites--are not well suited to undergo an abdominal MRI study at 3.0 T.

title: Diffusion measurements in intracranial hematomas: implications for MR imaging of acute stroke.
abstract: The purpose of our study was to analyze the diffusion properties of intracranial hematomas to understand the effects of hematomas on diffusion-weighted MR images of patients with acute stroke and to further our understanding of the evolution of signal intensities of hematomas on conventional MR images. We hypothesized that hematomas containing blood with intact RBC membranes (ie, early hematomas) have restricted diffusion compared with hematomas in which RBC membranes have lysed.



Seventeen proven intracranial hematomas were studied with conventional and diffusion MR imaging. Hematomas were characterized using conventional images to determine the stage of evolution and their putative biophysical composition, as described in the literature. Apparent diffusion coefficient (ADC) measurements for each putative hematoma constituent (intracellular oxyhemoglobin, intracellular deoxyhemoglobin, intracellular methemoglobin, and extracellular methemoglobin) were compared with each other and with normal white matter.



Hematomas showing hemoglobin within intact RBCs by conventional MR criteria (n = 14) showed equivalent ADC values, which were reduced compared with hematomas containing lysed RBCs (P = .0029 to .024). Compared with white matter, hematomas containing lysed RBCs had higher ADC measurements (P = .003), whereas hematomas containing intact RBCs had reduced ADC measurements (P < .0001).



Restricted diffusion is present in early intracranial hematomas in comparison with both late hematomas and normal white matter. Therefore, early hematomas would be displayed as identical to the signal intensity of acute infarction on ADC maps, despite obvious differences on conventional MR images. These data also are consistent with the biochemical composition that has been theorized in the stages of evolving intracranial hematomas and provide further evidence that paramagnetic effects, rather than restriction of water movement, are the dominant cause for their different intensity patterns on conventional MR images.

title: Combined T2-weighted and diffusion-weighted MRI for localization of prostate cancer.
abstract: The objective of our study was to compare T2-weighted MRI alone and T2 combined with diffusion-weighted imaging (DWI) for the localization of prostate cancer.



T2-weighted imaging and DWI (b value = 600 s/mm2) were performed in 49 patients before radical prostatectomy using an endorectal coil at 1.5 T in this prospective trial. The peripheral zone of the prostate was divided into sextants and the transition zone into left and right halves. T2 images alone and then T2 images combined with apparent diffusion coefficient (ADC) maps (T2 + DWI) were scored for the likelihood of tumor and were compared with whole-mount histology results. Fixed window and level settings were used to display the ADC maps. Only tumors with an area of more than 0.13 cm2 (> 4 mm diameter) and a Gleason score of > or = 6 were considered significant. The area under the receiver operating characteristic curve (A(z)) was used to assess accuracy.



In the peripheral zone, the A(z) value was significantly higher (p = 0.004) for T2 plus DWI (A(z) = 0.89) than for T2 imaging alone (A(z) = 0.81). Performance was poorer in the transition zone for both T2 plus DWI (A(z) = 0.78) and T2 (A(z) = 0.79). For the whole prostate, sensitivity was significantly higher (p < 0.001) with T2 plus DWI (81% [120/149]) than with T2 imaging alone (54% [81/149]), with T2 plus DWI showing only a slight loss in specificity compared with T2 imaging alone (84% [204/243] vs 91% [222/243], respectively).



Combined T2 and DWI MRI is better than T2 imaging alone in the detection of significant cancer (Gleason score > or = 6 and diameter > 4 mm) within the peripheral zone of the prostate.

title: Ultra-high-b-value diffusion-weighted MR imaging for the detection of prostate cancer: evaluation in 201 cases with histopathological correlation
abstract: PurposeTo assess the diagnostic performance of diffusion-weighted magnetic resonance (MR) imaging (DWI) for prostate cancer detection, using different b-values. total of 201 patients who underwent MR imaging before total prostatectomy were evaluated. MR images were independently assessed by three radiologists. Three combinations of sequences were separately evaluated, as follows: group 1 [T2-weighted images (T2WI) alone], group 2 (T2WI and DWI with a b-value of 1,000 s/mm2), group 3 (T2WI and DWI with a b-value of 2,000 s/mm2). Whole-mount-section histopathological examination was the reference standard. Areas under the receiver operating characteristic curve (AUCs) and diagnostic performance parameters were determined.ResultsThe sensitivity, specificity, and AUC for the detection of prostate cancer were as follows: 52.2%, 80.7%, and 0.694 in group 1; 61.2%, 82.6%, and 0.755 in group 2; 73.2%, 89.7%, and 0.842 in group 3. Group 3 achieved the highest diagnostic performance, followed by group 2 (P < 0.05). In the transition zone, the specificity was lower (P < 0.001) for group 2 (82.2%) than for group 1 (86.2%).ConclusionThe addition of diffusion-weighted images with a b-value of 2,000 s/mm2 to T2WI can improve the diagnostic performance of MR imaging in prostate cancer detection.

title: Thirty-Two-Channel Coil 3T Magnetic Resonance-Guided Biopsies of Prostate Tumor Suspicious Regions Identified on Multimodality 3T Magnetic Resonance Imaging: Technique and Feasibility
abstract: To test the technique and feasibility of translating tumor suspicious region maps in the prostate, obtained by multimodality, anatomic, and functional 3T magnetic resonance imaging (MRI) data to 32-channel coil, T2-weighted (T2-w), 3T MR images, for directing MR-guided biopsies. Furthermore, to evaluate the practicability of MR-guided biopsy on a 3T MR scanner using a 32-channel coil and a MR-compatible biopsy device. Twenty-one patients with a high prostate-specific antigen (>4.0 ng/mL) and at least 2 prior negative transrectal ultrasound-guided biopsies of the prostate underwent an endorectal coil 3T MRI, which included T2-w, diffusion weighted and dynamic contrast enhanced MRI. From these multimodality images, tumor suspicious regions (TSR) were determined. The 3D localization of these TSRs within the prostatic gland was translated to the T2-w MR images of a subsequent 32-channel coil 3T MRI. These were then biopsied under 3T MR guidance. In all patients, TSRs could be identified and accurately translated to subsequent 3T MR images and biopsied under MR guidance. Median MR biopsy procedure time was 35 minutes. Of the 21 patients, 8 (38%) were diagnosed with prostate cancer, 6 (29%) had evidence of prostatitis, 6 (29%) had combined inflammatory and atrophic changes, and only 1 (5%) patient had no identifiable pathology. Multimodality, 3T MRI determined TSRs could effectively be translated to T2-weighted images, to be used for MR biopsies. 3T MR-guided biopsy based on these translated TSRs was feasible, performed in a clinical useful time, and resulted in a high number of positive results.

title: Diagnostic performance of diffusion-weighted magnetic resonance imaging in bladder cancer: potential utility of apparent diffusion coefficient values as a biomarker to predict clinical aggressiveness
abstract: diagnostic performance of diffusion-weighted magnetic resonance imaging (DW-MRI) in bladder cancer and the potential role of apparent diffusion coefficient (ADC) values in predicting pathological bladder cancer phenotypes associated with clinical aggressiveness were investigated.MethodsOne hundred and four bladder cancer patients underwent DW-MRI and T2-weighted magnetic resonance imaging (T2W-MRI) before transurethral resection. The image sets were reviewed by two independent radiologists. ADC values were measured in 121 eligible tumours.ResultsIn detecting patients with bladder cancer, DW-MRI exhibited high sensitivity equivalent to that of T2W-MRI (>90%). Interobserver agreement was excellent for DW-MRI (κ score, 0.88) though moderate for T2W-MRI (0.67). ADC values were significantly lower in high-grade (vs. low-grade, P < 0.0001) and high-stage (T2 vs. T1 vs. Ta, P < 0.0001) tumours. At a cut-off ADC value determined by partition analysis, clinically aggressive phenotypes including muscle-invasive bladder cancer (MIBC) and high-grade T1 disease were differentiated from less aggressive phenotypes with a sensitivity of 88%, a specificity of 85% and an accuracy of 87%.ConclusionDW-MRI exhibits high diagnostic performance in bladder cancer with excellent objectivity. The ADC value could potentially serve as a biomarker to predict clinical aggressiveness in bladder cancer.

title: Hypointensity on diffusion-weighted MRI of the brain related to T2 shortening and susceptibility effects.
abstract: 1705 ecause diffusion-weighted images are inherently T2-weighted, changes in tissue T2 can influence the appearance of diffusion-weighted images independent of tissue diffusibility. The effect of prolonged T2—that is, of T2 “shine-through”—is well known. Less well described are the effects of T2 shortening on the appearance of diffusion-weighted images. The goal of this article is to show examples of how T2 shortening influences the appearance of diffusion-weighted images.

title: [Diffusion-weighted MR imaging of the brain].
abstract: Imaging of water diffusion or diffusion-weighted MR imaging provides physiological information about brain diseases that cannot be obtained from conventional sequences. This technique is very sensitive for the detection of cerebral ischemia from arterial origin and can distinguish cerebral ischemia from other non-vascular brain pathologies in patients presenting with abrupt onset of focal neurological deficit. Diffusion-weighted imaging is used for the evaluation of non-vascular diseases as well. Combined with conventional sequences, it is helpful to differentiate brain abscesses from necrotic tumors. Quantitative diffusion-weighted imaging provides additional information in the characterization of tumors or inflammatory, degenerative and metabolic lesions. Finally, diffusion-weighted imaging data also has prognostic value.

title: Comparison of cystoscopy with diffusion-weighted magnetic resonance images used in the diagnosis and follow-up of patients with bladder tumors.
abstract: To compare diffusion-weighted magnetic resonance imaging (DW-MRI) with cystoscopy in the diagnosis and follow-up of patients with bladder tumor and to investigate any histopathological correlation.



Totally 59 patients, between 31-85 years (mean age 60∓13) referred to our clinic due to a hematuria complaint were enrolled and evaluated by upper urinary system pathology and then DW-MRI (average 7 days) and cystoscopy. Apparent diffusion coefficients (ADCs) of images were calculated.



While a mass in bladder was determined with cystoscopy in 43 out of 59 patients,the mass was not determined in 16 of the patients (n=34 malign, n=9 benign). While a mass was determined in 40 out of 59 patients with DW-MRI,the mass was not determined in 19 of the patients(n=40 malign, n=19 benign). Regarding ADC values, mean ADC values of 34 patients who were diagnosed with a bladder tumor (1.05∓0.22x10(-3) mm2/s), were significantly lower than the mean ADC values obtained from the normal bladder wall (1.830∓0.18x10(-3) mm2/s) whereas a statistically significant difference was found (p<0.001). ADC values in 9 patients with a benign lesion (1.73∓0.12x10(-3) mm2/s), were not found statistically different from the mean ADC values obtained from the normal bladder wall (1.78∓0.2x10(-3) mm2/s) (p>0.05). A significant difference was determined between ADC values of benign lesions and the ADC values of malign lesions (p<0.001).



According to cystoscopy, values of DW-MRI's related with sensitivity, specificity and accuracy were found, respectively 90%, 93% and 91%. As the DW-MRI is a non-invasive and a rapid technique, and does not contain ionized radiation and because it is accepted as an important marker of tumor cellularity, it may be used as an alternative in future diagnosis and follow-up of bladder tumors.

title: Carcinosarcoma of the urinary bladder: dynamic contrast-enhanced MR imaging with clinical and pathologic correlation.
abstract: This article describes the MR imaging features of carcinosarcoma of the urinary bladder with clinical presentation and pathologic correlation in three adults.



Carcinosarcoma of the urinary bladder is a rare and aggressive tumor that has a clinical presentation similar to that of transitional cell carcinoma of the bladder. Dynamic gadolinium-enhanced MR imaging features are discussed.

title: Preoperative T staging of urinary bladder cancer: does diffusion-weighted MRI have supplementary value?
abstract: The objective of our study was to evaluate whether diffusion-weighted MRI has supplementary value in the preoperative T staging of urinary bladder cancer.



Nineteen consecutive patients (18 men and one woman; age range, 55-83 years; mean, 71 years) known to have or suspected of having urinary bladder cancer underwent MRI at our institution. Urinary bladder cancer was pathologically proven in 18 patients. The pathologic stages were T1 in 14 patients, T2 in two, T3 in one, and T4 in one. Three separate MR image sets were retrospectively reviewed by two independent radiologists: unenhanced T1-weighted images (TR/TE, 607/10) and T2-weighted images (TR(eff)/TE(eff), 4,415/100); unenhanced T1-weighted, T2-weighted, and gadolinium-enhanced images (TR/TE, 10/4.2); and unenhanced T1-weighted, T2-weighted, and diffusion-weighted images (TR(eff)/TE(eff), 2,191/69; b factor, 1,000 s/mm(2)). The radiologists, who were blinded to the pathology findings, assigned T stages and confidence levels for tumors of stage T2 or greater. We used pathologic stages documented in the official pathologic reports as the standard of reference. Observer performance was tested using Spearman's rank correlation, the McNemar test, and receiver operating characteristic (ROC) curve analysis.



The correlation between the radiologic and pathologic stages was greater with the diffusion sequence (rho = 0.66) than with the unenhanced (0.62) or gadolinium-enhanced (0.62) sequence (p = 0.34). The sensitivity, specificity, accuracy, and area under the ROC curve for tumors of stage T2 or greater were 80%, 79%, 79%, and 0.71 for the unenhanced sequence; 80%, 79%, 79%, and 0.77 for the gadolinium sequence; and 40%, 93%, 79%, and 0.56 for the diffusion-weighted sequence, respectively (p > 0.05).



Our results suggest that diffusion-weighted MRI might have high specificity for the detection of invasive urinary bladder tumors. Patients with suspected urinary bladder carcinomas may well be evaluated by MRI including diffusion-weighted imaging for better preoperative T staging.

title: Clinical value of T2-weighted imaging combined with diffusion-weighted imaging in preoperative T staging of urinary bladder cancer: a large-scale, multiobserver prospective study on 3.0-T MRI.
abstract: To prospectively assess the incremental value of diffusion-weighted imaging (DWI) combined with T2-weighted images (T2WI) in determining the T stage of bladder cancer by using pathologic findings as the reference standard.



This study is approved by the institutional review board; informed consent was waived. The study includes 362 patients (age range, 48-87 years; mean, 71 years) who underwent 3.0-T magnetic resonance imaging and histologic examination. Three observers with varying experience levels reviewed the T2WI data alone, DWI data alone, and combined T2WI and DWI data. Sensitivity, specificity, accuracy, and area under curve (AUC) were determined with the Z test after adjusting for data clustering.



For differentiating Tis to T1 tumors from T2 to T4 tumors, the AUCs for T2WI and DWI (0.97 for observer 1 and 0.96 for observer 2) were greater than those for the DWI alone (0.92 for observer 1 and 0.90 for observer 2) (P < .05). Observer 3 had similar AUCs for T2WI and DWI compared to DWI alone. The accuracy of T2WI and DWI (observer 1, 98%; observer 2, 96%; observer 3, 92%) was greater than that of DWI alone (observer 1, 92%; observer 2, 90%; observer 3, 87%) for all observers (P < .05). The specificity of T2WI and DWI (observer 1, 100%; observer 2, 98%; observer 3, 93%) was greater than that of DWI alone (observer 1, 92%; observer 2, 90%; observer 3, 87%) for all observers (P < .05). Sensitivity was not improved even when T2WI and DWI were used. For differentiating Tis to T2 Tumors from T3 to T4 Tumors, the overall accuracy, specificity, and AUC for diagnosing T2 or higher stages were not significantly improved by combiningT2WI and DWI.



T2WI combined with DWI can be a reliable sequence for preoperative evaluation of T stage urinary bladder cancer. It is particularly more useful in differentiating T1 or lower tumors from T2 or higher tumors compared to DWI alone.

title: Histopathological analysis of a bladder cancer stalk observed on MRI.
abstract: Papillary transitional cell carcinoma of the bladder has a loose connective tissue stalk. For staging of bladder cancer on magnetic resonance imaging (MRI), it is important to clearly separate the cancer from the bladder wall. It is possible to distinguish a stalk from the cancer by the difference of intensity on the using MRI. Sixteen stalks of 20 polypoid bladder tumors on any of the T(2)W(I), dynamic images and delayed enhanced images were demonstrated. Most of the stalks show lower signal intensity than the tumors on T(2)W(I), less enhancement on dynamic images and stronger enhancement on delayed enhanced images. The stalk consisted of fibrous connective tissue, capillary blood vessels, inflammatory cell infiltration and edema. This stalk extended from the bladder wall to the center of the tumor. Some of the superficial muscular bundles were pulled into the stalk. These histopathological findings were compatible with the patterns of signal intensities on MRI. The identification of the stalk of a polypoid tumor may be an important observation to exclude bladder wall invasion by tumor.

title: Preoperative T staging of urinary bladder cancer: efficacy of stalk detection and diagnostic performance of diffusion-weighted imaging at 3T.
abstract: We evaluated the ability of diffusion-weighted imaging (DWI) at 3 tesla for diagnosing T stage and detecting stalks in bladder cancer.



In total, 39 consecutive patients with bladder tumors underwent magnetic resonance (MR) imaging that included T2-weighted imaging (T2WI) and DWI using a 3T MR scanner. Two radiologists interpreted T2WI plus DWI and T2WI for diagnosis of T stage and for detection of stalks. We used McNemar's test to examine differences in diagnostic performance and Fisher's exact test to evaluate differences in stalk detection frequency.



Specificity and accuracy in differentiating T1 tumors from T2 to T4 tumors were significantly better with T2WI plus DWI (83% [20/24] and 85% [33/39]) than T2WI (50% [12/24] and 67% [26/39]; P = 0.02), and accuracy for diagnosing tumor stage was significantly better with T2WI plus DWI (82% [32/39]) than T2WI alone (59% [23/39]; P = 0.03). The observers identified stalks in 11 tumors by T2WI (48% [11/23]) and 17 by DWI (74% [17/23]) (P < 0.03).



DWI at 3T was superior to T2WI for evaluating the T stage of bladder cancer, particularly in differentiating T1 tumors from those T2 or higher, and in detecting stalks of papillary bladder tumors.

title: Urinary bladder cancer: role of MR imaging.
abstract: Urinary bladder cancer is a heterogeneous disease with a variety of pathologic features, cytogenetic characteristics, and natural histories. It is the fourth most common cancer in males and the tenth most common cancer in females. Urinary bladder cancer has a high recurrence rate, necessitating long-term surveillance after initial therapy. Early detection is important, since up to 47% of bladder cancer-related deaths may have been avoided. Conventional computed tomography (CT) and magnetic resonance (MR) imaging are only moderately accurate in the diagnosis and local staging of bladder cancer, with cystoscopy and pathologic staging remaining the standards of reference. However, the role of newer MR imaging sequences (eg, diffusion-weighted imaging) in the diagnosis and local staging of bladder cancer is still evolving. Substantial advances in MR imaging technology have made multiparametric MR imaging a feasible and reasonably accurate technique for the local staging of bladder cancer to optimize treatment. In addition, whole-body CT is the primary imaging technique for the detection of metastases in bladder cancer patients, especially those with disease that invades muscle.

title: Potential and limitations of diffusion-weighted magnetic resonance imaging in kidney, prostate, and bladder cancer including pelvic lymph node staging: a critical analysis of the literature.
abstract: Diagnosis, staging, and treatment monitoring are still suboptimal for most genitourinary tumours. Diffusion-weighted magnetic resonance imaging (DW-MRI) has already shown promise as a noninvasive imaging modality in the early detection of microstructural and functional changes in several pathologies of various organs.



To assess the potential and limitations of DW-MRI in the management of patients with kidney, prostate, and bladder cancer.



A nonsystematic literature search using the Medline/PubMed and Embase databases for full-length papers reporting on DW-MRI for kidney, prostate, and bladder cancer was performed up to August 1, 2011. Only those articles with complete data reporting on DW-MRI applications with potential implications in solving commonly encountered clinical challenges relating to tumour detection, staging, and treatment monitoring were finally examined.



For kidney tumours DW-MRI is a reasonable alternative to conventional cross-sectional imaging to detect and characterise focal renal lesions, especially in patients with impaired renal function. For prostate cancer, DW-MRI applied in addition to conventional T2-weighted and contrast-enhanced magnetic resonance imaging (MRI) improves tumour detection and localisation. In addition, it has shown promise for the assessment of tumour aggressiveness and for treatment monitoring during active surveillance, radiation therapy, and focal therapy. For bladder cancer, DW-MRI may improve the performance of conventional T2-weighted and contrast-enhanced MRI in the work-up of bladder cancer, helping to differentiate non-muscle-invasive from muscle-invasive tumours. For pelvic lymph nodes, initial results showed the potential to improve nodal staging of prostate and bladder cancer compared with conventional cross-sectional imaging.



DW-MRI holds promise to ameliorate the management of patients with kidney, prostate, and bladder cancer including pelvic lymph node staging. Current limitations include the lack of standardisation of the technique across multiple centres and the still limited expertise.

title: Diffusion‐weighted magnetic resonance imaging in patients selected for radical cystectomy: detection rate of pelvic lymph node metastases
abstract: Study Type – Diagnostic (exploratory cohort)

title: Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging facilitates detection of metastases in normal-sized pelvic lymph nodes of patients with bladder and prostate cancer.
abstract: Conventional cross-sectional imaging with computed tomography and magnetic resonance imaging (MRI) has limited accuracy for lymph node (LN) staging in bladder and prostate cancer patients.



To prospectively assess the diagnostic accuracy of combined ultrasmall superparamagnetic particles of iron oxide (USPIO) MRI and diffusion-weighted (DW) MRI in staging of normal-sized pelvic LNs in bladder and/or prostate cancer patients.



Examinations with 3-Tesla MRI 24-36 h after administration of USPIO using conventional MRI sequences combined with DW-MRI (USPIO-DW-MRI) were performed in 75 patients with clinically localised bladder and/or prostate cancer staged previously as N0 by conventional cross-sectional imaging. Combined USPIO-DW-MRI findings were analysed by three independent readers and correlated with histopathologic LN findings after extended pelvic LN dissection (PLND) and resection of primary tumours.



Sensitivity and specificity for LN status of combined USPIO-DW-MRI versus histopathologic findings were evaluated per patient (primary end point) and per pelvic side (secondary end point). Time required for combined USPIO-DW-MRI reading was assessed.



At histopathologic analysis, 2993 LNs (median: 39 LNs; range: 17-68 LNs per patient) with 54 LN metastases (1.8%) were found in 20 of 75 (27%) patients. Per-patient sensitivity and specificity for detection of LN metastases by the three readers ranged from 65% to 75% and 93% to 96%, respectively; sensitivity and specificity per pelvic side ranged from 58% to 67% and 94% to 97%, respectively. Median reading time for the combined USPIO-DW-MRI images was 9 min (range: 3-26 min). A potential limitation is the absence of a node-to-node correlation of combined USPIO-DW-MRI and histopathologic analysis.



Combined USPIO-DW-MRI improves detection of metastases in normal-sized pelvic LNs of bladder and/or prostate cancer patients in a short reading time.

title: Metastases in normal-sized pelvic lymph nodes: detection with diffusion-weighted MR imaging.
abstract: To prospectively assess the diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging in the detection of pelvic lymph node metastases in patients with prostate and/or bladder cancer staged as N0 with preoperative cross-sectional imaging.



This study was approved by an independent ethics committee. Written informed consent was obtained from all patients. Patients with no enlarged lymph nodes on preoperative cross-sectional images who were scheduled for radical resection of the primary tumor and extended pelvic lymph node dissection were enrolled. All patients were examined with a 3-T MR unit, and examinations included conventional and DW MR imaging of the entire pelvis. Image analysis was performed by three independent readers blinded to any clinical information. Metastases were diagnosed on the basis of high signal intensity on high b value DW MR images and morphologic features (shape, border). Histopathologic examination served as the standard of reference. Sensitivity and specificity were calculated, and bias-corrected 95% confidence intervals (CIs) were obtained with the bootstrap method. The Fleiss and Cohen κ and median test were applied for statistical analyses.



A total of 4846 lymph nodes were resected in 120 patients. Eighty-eight lymph node metastases were found in 33 of 120 patients (27.5%). Short-axis diameter of these metastases was less than or equal to 3 mm in 68, more than 3 mm to 5 mm in 13, more than 5 mm to 8 mm in five; and more than 8 mm in two. On a per-patient level, the three readers correctly detected metastases in 26 (79%; 95% CI: 64%, 91%), 21 (64%; 95% CI: 45%, 79%), and 25 (76%; 95% CI: 60%, 90%) of the 33 patients with metastases, with respective specificities of 85% (95% CI: 78%, 92%), 79% (95% CI: 70%, 88%), and 84% (95% CI: 76%, 92%). Analyzed according to hemipelvis, lymph node metastases were detected with histopathologic examination in 44 of 240 pelvic sides (18%); the three readers correctly detected these on DW MR images in 26 (59%; 95% CI: 45%, 73%), 19 (43%; 95% CI: 27%, 57%), and 28 (64%; 95% CI: 47%, 78%) of the 44 cases.



DW MR imaging enables noninvasive detection of small lymph node metastases in normal-sized nodes in a substantial percentage of patients with prostate and bladder cancer diagnosed as N0 with conventional cross-sectional imaging techniques.

title: Combined ultrasmall superparamagnetic particles of iron oxide-enhanced and diffusion-weighted magnetic resonance imaging reliably detect pelvic lymph node metastases in normal-sized nodes of bladder and prostate cancer patients.
abstract: Lymph node staging of bladder or prostate cancer using conventional imaging is limited. Newer approaches such as ultrasmall superparamagnetic particles of iron oxide (USPIO) and diffusion-weighted magnetic resonance imaging (DW-MRI) have inconsistent diagnostic accuracy and are difficult to interpret.



To assess whether combined USPIO and DW-MRI (USPIO-DW-MRI) improves staging of normal-sized lymph nodes in bladder and/or prostate cancer patients.



Twenty-one consecutive patients with bladder and/or prostate cancer were enrolled between May and October 2008. One patient was excluded secondary to bone metastases detected on DW-MRI with subsequent abstention from surgery.



Patients preoperatively underwent 3-T MRI before and after administration of lymphotropic USPIO using conventional MRI sequences combined with DW-MRI. Surgery consisted of extended pelvic lymphadenectomy and resection of primary tumors.



Diagnostic accuracies of the new combined USPIO-DW-MRI approach compared with the "classic" reading method evaluating USPIO images without and with DW-MRI versus histopathology were evaluated. Duration of the two reading methods was noted for each patient.



Diagnostic accuracy (90% per patient or per pelvic side) was comparable for the classic and the USPIO-DW-MRI reading method, while time of analysis with 80 min (range 45-180 min) for the classic and 13 min (range 5-90 min) for the USPIO-DW-MRI method was significantly shorter (p<0.0001). Interobserver agreement (three blinded readers) was high with a kappa value of 0.75 and 0.84, respectively. Histopathological analysis showed metastases in 26 of 802 analyzed lymph nodes (3.2%). Of these, 24 nodes (92%) were correctly diagnosed as positive on USPIO-DW-MRI. In two patients, one micrometastasis each (1.0x0.2 mm; 0.7x0.4 mm) was missed in all imaging studies.



USPIO-DW-MRI is a fast and accurate method for detecting pelvic lymph node metastases, even in normal-sized nodes of bladder or prostate cancer patients.

title: Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study.
abstract: There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage.



Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed.



Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%).



Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

title: Extracapsular Extension of Pelvic Lymph Node Metastases From Urothelial Carcinoma of the Bladder Is an Independent Prognostic Factor
abstract: To analyze the prognostic impact of risk factors for urothelial carcinoma of the bladder (UCB) with pelvic lymph node (LN) metastases.  We analyzed a consecutive series of 507 patients with UCB who were preoperatively staged N0M0. One hundred one of 124 eligible patients who were treated with radical cystectomy and standardized extended bilateral pelvic lymphadenectomy with curative intent and had postoperatively confirmed LN metastases were evaluated in regard to recurrence-free and overall survival.  A median of 22 nodes per patient (range, 10 to 43 nodes) were removed and examined. Median recurrence-free and overall survival durations were 17 months and 21 months (range for both, 1 to 191 months), respectively. In the multivariate analysis for recurrence-free survival, extracapsular extension of LN metastases was the strongest prognostic factor (P = .019). Other variables such as tumor stage (pT1/2 v pT3 and pT4), the number (< five v ≥ five), and the percentage (< 20...

title: Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure?
abstract: In prostate cancer involvement of regional lymph nodes is regarded as a poor prognostic factor. Is this also true for micrometastasis if a meticulous lymph node dissection is performed? We determined progression rate and survival of patients with positive nodes following radical prostatectomy according to the number of metastases.



Between 1989 and 1999, 367 patients with clinically organ confined prostate cancer underwent meticulous pelvic lymph node dissection and radical prostatectomy. None of the patients received immediate adjuvant therapy.



Of the patients 92 (25%) had histologically proven lymph node metastases. Followup of more than 1 year was available in 88 patients (96%), and median followup was 45 months (range 13 to 141). Of 19 patients (22%) who died of prostate cancer 16 had more than 1 positive node. Of the 39 patients with only 1 positive node 15 (39%) remained without signs of clinical or chemical progression. Whereas of the 20 and 29 patients with 2 or more positive lymph nodes only 2 (10%) and 4 (14%), respectively, remained disease-free. Time to prostate specific antigen relapse, symptomatic progression and tumor related death were significantly affected by the number of positive nodes.



Meticulous lymph node dissection reveals a high rate of metastases (25%). In patients with positive nodes time to progression is significantly correlated with the number of diseased nodes. Some patients with minimal metastatic disease remain free of prostate specific antigen relapse for more than 10 years after prostatectomy without any adjuvant treatment. Meticulous pelvic lymph node dissection, particularly in patients with micrometastases, seems not only to be a staging procedure, but may also have a positive impact on disease progression and long-term disease-free survival.

title: Good outcome for patients with few lymph node metastases after radical retropubic prostatectomy.
abstract: Conflicting results exist regarding the value of an extended pelvic lymph node dissection (PLND) in node-positive patients undergoing radical retropubic prostatectomy (RRP) for clinically localized prostate cancer.



To assess the long-term outcome in node-positive patients who underwent extended PLND followed by RRP.



A consecutive series of 122 node positive patients with negative preoperative staging examinations, no neoadjuvant hormonal or radiotherapy, and who underwent extended PLND (>/=10 lymph nodes in the surgical specimen) followed by RRP were analyzed. None of the patients received immediate androgen deprivation therapy (ADT).



All patients underwent extended PLND followed by RRP.



Biochemical recurrence-free survival, cancer-specific, and overall survival were assessed using the Kaplan-Meier technique.



Median prostate-specific antigen (PSA) was 16ng/ml. At pathological examination 76% of the 122 patients had pT3-pT4 tumours, 50% seminal vesicle infiltration. A median of 22 nodes were removed per patient. Median cancer-specific survival at 5 and 10 yr was 84.5% and 60.1%, respectively. In patients with </=2 or >/=3 positive nodes removed, median cancer-specific survival at 10 yr was 78.6% and 33.4%, respectively (p<0.001). After a median period of 33 mo, 61 of the 122 patients (50%) received ADT, particularly those (69%) with >/=3 positive nodes removed. This retrospective study includes a significant percentage of patients with high tumour burden, and therefore may not reflect current patient series.



Patients with </=2 positive nodes detected after extended PLND followed by RRP had good long-term results and should not be denied treatment with curative intent. In contrast, prognosis was poor in patients with >/=3 positive nodes, despite extended PLND and despite ADT in 69% of patients.

title: TECHNICAL ARTICLE: Fusion of high b‐value diffusion‐weighted and T2‐weighted MR images improves identification of lymph nodes in the pelvis
abstract: Accurate identification of lymph nodes facilitates nodal assessment by size, morphological or MR lymphographic criteria. We compared the MR detection of lymph nodes in patients with pelvic cancers using T2‐weighted imaging, and fusion of diffusion‐weighted imaging (DWI) and T2‐weighted imaging.

title: Whole‐body MRI including diffusion‐weighted imaging (DWI) for patients with recurring prostate cancer: Technical feasibility and assessment of lesion conspicuity in DWI
abstract: To evaluate the principal methodological aspects of whole‐body magnetic resonance imaging (MRI) including diffusion‐weighted imaging (DWI) with background suppression using a time‐optimized protocol for restaging of prostate cancer patients in a technical feasibility study.

title: Clinicopathologic significance of high signal intensity on diffusion-weighted MR imaging in the ureter, urethra, prostate and bone of patients with bladder cancer.
abstract: The aim of this study was to determine the clinicopathologic significance of high-intensity areas in the ureter, urethra, prostate, and bone incidentally found on diffusion-weighted magnetic resonance imaging (DWI) for the staging of bladder cancer.



Axial and sagittal DWI and T2-weighted imaging of the pelvis were evaluated in 157 patients with bladder cancer. Two observers assessed T2-weighted imaging with DWI independently. The observers pointed out 67 areas showing abnormal high signal intensity on DWI in the ureter (n = 17), urethra (n = 8), prostate (n = 20), and bone (n = 22). Of the 67 high-intensity areas, 33 lesions were confirmed histopathologically (ureter, n = 10; urethra, n = 7; prostate, n = 16), and 22 bone lesions were diagnosed using T1-weighted imaging and follow-up computed tomography. Thus, 55 lesions were evaluable for correlation with DWI findings.



Of the 55 high-intensity areas, 28 (53%) were synchronous or metastatic urothelial cancer or invasion of urothelial cancer. The remaining 27 (47%) were a ureteral clot in one, a ureteral stone granuloma in one, prostatic cancer in six, granulomatous prostatitis in three, and normal red bone marrow in 16.



DWI is useful to comprehend the extent of bladder cancer and to detect incidentally coexisting diseases. Other imaging, endoscopic, and clinical findings would be useful to reduce false positivity.

title: Magnetic resonance imaging of bone marrow in oncology, Part 1
abstract: Magnetic resonance imaging plays an integral role in the detection and characterization of marrow lesions, planning for biopsy or surgery, and post-treatment follow-up. To evaluate findings in bone marrow on MR imaging, it is essential to understand the normal composition and distribution of bone marrow and the changes in marrow that occur with age, as well as the basis for the MR signals from marrow and the factors that affect those signals. The normal distribution of red and yellow marrow in the skeleton changes with age in a predictable sequence. Important factors that affect MR signals and allow detection of marrow lesions include alterations in fat–water distribution, destruction of bony trabeculae, and contrast enhancement. This two-part article reviews and illustrates these issues, with an emphasis on the practical application of MR imaging to facilitate differentiation of normal marrow, tumor, and treatment-related marrow changes in oncology patients.

title: Whole-body diffusion-weighted MR imaging in cancer: current status and research directions.
abstract: Diffusion-weighted (DW) magnetic resonance (MR) imaging is emerging as a powerful clinical tool for directing the care of patients with cancer. Whole-body DW imaging is almost at the stage where it can enter widespread clinical investigations, because the technology is stable and protocols can be implemented for the majority of modern MR imaging systems. There is a continued need for further improvements in data acquisition and analysis and in display technologies. Priority areas for clinical research include clarification of histologic relationships between tissues of interest and DW MR imaging biomarkers at diagnosis and during therapy response. Because whole-body DW imaging excels at bone marrow assessments at diagnosis and for therapy response, it can potentially address a number of unmet clinical and pharmaceutical requirements. There are compelling needs to document and understand how common and novel treatments affect whole-body DW imaging results and to establish response criteria that can be tested in prospective clinical studies that incorporate measures of patient benefit.

title: Relationship between bone marrow cellularity and apparent diffusion coefficient
abstract: This study was performed to determine if there is a relationship between apparent diffusion coefficient (ADC) and cellularity of bone marrow of the posterior ilium. Four groups of various marrow cellularity underwent diffusion‐weighted echo‐planar imaging: 1) adults with normal hypocellularity (21 patients); 2) adults with normal normocellularity (13 patients); 3) young children with normal hypercellularity (5 patients); and 4) adults with lymphoma‐related hypercellularity (3 patients). In all adults, marrow cellularity was confirmed by uni‐or bilateral bone marrow biopsies. In children, the iliac marrow was presumed hypercellular because of their ages. A total of 66 ADC values of bone marrow calculated from diffusion‐weighted images with b‐values of 30 and 300 seconds/mm2 was evaluated. Hypercellular marrow (normal and lymphoma‐related) showed the highest mean ADC, and hypocellular the lowest ADC. Statistically significant differences were found between three groups of normal marrow: hypocellular, normocellular, and hypercellular. There is a positive correlation between ADC and cellularity of bone marrow.  Imaging 2001;13:757–760.

title: Diagnostic value of whole‐body magnetic resonance imaging for bone metastases: a systematic review and meta‐analysis
abstract: To assess the overall diagnostic accuracy of whole‐body magnetic resonance imaging (WB‐MRI) in detecting bone metastases with a meta‐analysis.

title: Whole-body MRI for the staging and follow-up of patients with metastasis.
abstract: The advent of whole-body MRI (WB-MRI) has introduced tumor imaging with a systemic approach compared to established sequential, multi-modal diagnostic algorithms. Hardware innovations, such as the introduction of multi-receiver channel whole-body scanners at 1.5 T and recently 3T, combined with acquisition acceleration techniques, have made high resolution WB-MRI clinically feasible. Now, a dedicated assessment of individual organs with various soft tissue contrast, spatial resolution and contrast media dynamics can be combined with whole-body anatomic coverage in a multi-planar imaging approach. More flexible protocols, e.g. including T1-weighted TSE- and STIR-imaging, dedicated lung imaging or dynamic contrast-enhanced studies of the abdomen can be performed within less than 45 min. For initial tumor staging PET-CT as a competing whole-body modality in oncologic imaging has proved more accurate for the definition of T-stage and lymph node assessment, using the additional metabolic information of PET for the assessment of tumor viability and therapy response. However, new applications, such as MR-whole-body diffusion imaging, may significantly increase sensitivity in near future. WB-MRI has shown advantages for the detection of distant metastatic disease, especially from tumors frequently spreading to the liver or brain and it is especially useful as a radiation-free alternative for the surveillance of tumor patients with multiple follow-up exams. Furthermore, it has been introduced as a whole-body bone marrow screening application. Within this context WB-MRI is highly accurate for the detection of skeletal metastases and staging of hematologic diseases, such as multiple myeloma or lymphoma. This article summarizes recent developments and applications of WB-MRI and highlights its performance within the scope of systemic oncologic staging and surveillance.

title: Bone metastases from prostate, breast and multiple myeloma: differences in lesion conspicuity at short-tau inversion recovery and diffusion-weighted MRI.
abstract: The objective of this study was to compare the relative conspicuity of bone metastases on short-tau inversion recovery (STIR) and diffusion-weighted MRI (DWI) whole-body MR sequences for breast, prostate and myeloma malignancies.



44 whole-body MRI scans were reviewed retrospectively (coronal T(1) weighted, STIR and DWI with b=800). On each scan, up to four of the largest bone lesions were identified on T(1) weighting, and the region of interest signal intensity was measured on STIR and DWI, as well as the background signal intensity. The mean lesion signal to background ratio was calculated for each patient and then for each malignancy group.



In prostate cancer patients, the DWI signal/background ratio was greater than that of STIR in 22 out of 24 patients (mean DWI lesion/background ratio 3.91, mean STIR lesion/background ratio 2.31; p=0.0001). In multiple myeloma, the DWI ratio was higher in 6/7 patients (DWI group mean ratio 7.59, STIR group mean ratio 3.7; p=0.0366). In 13 breast cancer patients, mean STIR and DWI signal/background were similar (DWI group mean ratio 4.13, group mean STIR ratio 4.26; p=0.8587).



Bone lesion conspicuity measured by lesion/background signal intensity was higher on DWI b=800 than on STIR in patients with prostate cancer and multiple myeloma. DWI should be used in whole-body MR oncology protocols in these conditions to maximise lesion detection.

title: Bony metastases: assessing response to therapy with whole-body diffusion MRI
abstract: There are no universally accepted methods for assessing tumour response in skeletal sites with metastatic disease; response is assessed by a combination of imaging tests, serum and urine biochemical markers and symptoms assessments. Whole-body diffusion magnetic resonance imaging excels at bone marrow assessments at diagnosis and for therapy evaluations. It can potentially address unmet clinical and pharmaceutical needs for a reliable measure of tumour response. Signal intensity on high b-value images and apparent diffusion coefficient values can be related to underlying biophysical properties of skeletal metastases. Four patterns of change in response to therapy are described this review. Therapy response criteria need to be tested in prospective clinical studies that incorporate conventional measures of patient benefit.

title: Whole-body diffusion-weighted MRI: tips, tricks, and pitfalls.
abstract: We examine the clinical impetus for whole-body diffusion-weighted MRI and discuss how to implement the technique with clinical MRI systems. We include practical tips and tricks to optimize image quality and reduce artifacts. The interpretative pitfalls are enumerated, and potential challenges are highlighted.



Whole-body diffusion-weighted MRI can be used for tumor staging and assessment of treatment response. Meticulous technique and knowledge of potential interpretive pitfalls will help to avoid mistakes and establish this modality in radiologic practice.

title: Diffusion-weighted imaging (DWI) in musculoskeletal MRI: a critical review
abstract: Magnetic resonance imaging (MRI) is the mainstay of diagnosis, staging and follow-up of much musculoskeletal pathology. Diffusion-weighted magnetic resonance imaging (DWI) is a recent addition to the MR sequences conventionally employed. DWI provides qualitative and quantitative functional information concerning the microscopic movements of water at the cellular level. A number of musculoskeletal disorders have been evaluated by DWI, including vertebral fractures, bone marrow infection, bone marrow malignancy, primary bone and soft tissue tumours; post-treatment follow-up has also been assessed. Differentiation between benign and malignant vertebral fractures by DWI and monitoring of therapy response have shown excellent results. However, in other pathologies, such as primary soft tissue tumours, DWI data have been inconclusive in some cases, contributing little additional information beyond that gained from conventional MR sequences. The aim of this article is to critically review the current literature on the contribution of DWI to musculoskeletal MRI.

title: Role of apparent diffusion coefficients with diffusion-weighted magnetic resonance imaging in differentiating between benign and malignant bone tumors
abstract: BackgroundBenign and malignant bone tumors can present similar imaging features. This study aims to evaluate the significance of apparent diffusion coefficients (ADC) in differentiating between benign and malignant bone tumors. total of 187 patients with 198 bone masses underwent diffusion-weighted (DW) magnetic resonance (MR) imaging. The ADC values in the solid components of the bone masses were assessed. Statistical differences between the mean ADC values in the different tumor types were determined by Student’s t-test.ResultsHistological analysis showed that 84/198 (42.4%) of the bone masses were benign and 114/198 (57.6%) were malignant. There was a significant difference between the mean ADC values in the benign and malignant bone lesions (P <0.05). However, no significant difference was found in the mean ADC value between non-ossifying fibromas, osteofibrous dysplasia, and malignant bone tumors. When an ADC cutoff value ≥1.10 × 10−3 mm2/s was applied, malignant bone lesions were excluded with a sensitivity of 89.7%, a specificity of 84.5%, a positive predictive value of 82.6%, and a negative predictive value of 95.3%.ConclusionsThe combination of DW imaging with ADC quantification and T2-weighted signal characteristics of the solid components in lesions can facilitate differentiation between benign and malignant bone tumors.

title: Diffusion-weighted MR imaging for characterizing musculoskeletal lesions.
abstract: Diffusion-weighted (DW) imaging is a functional magnetic resonance (MR) imaging technique that can readily be incorporated into a routine non-contrast material-enhanced MR imaging protocol with little additional scanning time. DW imaging is based on changes in the Brownian motion of water molecules caused by tissue microstructure. The apparent diffusion coefficient (ADC) is a quantitative measure of Brownian movement: Low ADC values typically reflect highly cellular microenvironments in which diffusion is restricted by the presence of cell membranes, whereas acellular regions allow free diffusion and result in elevated ADC values. Thus, with ADC mapping, one may derive useful quantitative information regarding the cellularity of a musculoskeletal lesion using a nonenhanced technique. The role of localized DW imaging in differentiating malignant from benign osseous and soft-tissue lesions is still evolving; when carefully applied, however, this modality has proved helpful in a subset of tumor types, such as nonmyxoid soft-tissue tumors. Studies of the use of DW imaging in assessing the treatment response of both osseous and soft-tissue tumors have shown that higher ADC values correlate with better response to cytotoxic therapy. Successful application of DW imaging in the evaluation of musculoskeletal lesions requires familiarity with potential diagnostic pitfalls that stem from technical artifacts and confounding factors unrelated to lesion cellularity. Further investigation is needed to evaluate the impact of DW imaging-ADC mapping on management and outcome in patients with musculoskeletal lesions.

title: Diffusion-weighted imaging of bone marrow.
abstract: In diffusion-weighted magnetic resonance imaging (DWI-MRI), the observed MRI signal intensity is attenuated by the self-diffusion of water molecules. DWI can provide information about the microscopic structure and organization of biological tissue and thus can depict various pathological changes of organs or tissues. DWI has been successfully used for the characterization of bone marrow alterations or lesions, and in particular for the differentiation of benign and malignant vertebral compression fractures. In this review article, the basics of DWI are introduced, and several pulse sequences that have been used for DWI of the bone marrow are described. Subsequently, an extensive overview about diffusion studies of the bone marrow and in particular of DWI of vertebral compression fractures is provided.

title: Evaluation of diffusion‐weighted imaging for the differential diagnosis of poorly contrast‐enhanced and T2‐prolonged bone masses: Initial experience
abstract: To determine whether quantitative diffusion‐weighted imaging (DWI) is useful for characterizing poorly contrast‐enhanced and T2‐prolonged bone masses.

title: Diffusion and perfusion imaging of bone marrow.
abstract: In diffusion-weighted magnetic resonance imaging (DWI), the observed MRI signal intensity is attenuated by the self-diffusion of water molecules. DWI provides information about the microscopic structure and organization of a biological tissue, since the extent and orientation of molecular motion is influenced by these tissue properties. The most common method to measure perfusion in the body using MRI is T1-weighted dynamic contrast enhancement (DCE-MRI). The analysis of DCE-MRI data allows determining the perfusion and permeability of a biological tissue. DWI as well as DCE-MRI are established techniques in MRI of the brain, while significantly fewer studies have been published in body imaging. In recent years, both techniques have been applied successfully in healthy bone marrow as well as for the characterization of bone marrow alterations or lesions; e.g., DWI has been used in particular for the differentiation of benign and malignant vertebral compression fractures. In this review article, firstly a short introduction to diffusion-weighted and dynamic contrast-enhanced MRI is given. Non-quantitative and quantitative approaches for the analysis of DWI and semiquantitative and quantitative approaches for the analysis of DCE-MRI are introduced. Afterwards a detailed overview of the results of both techniques in healthy bone marrow and their applications for the diagnosis of various bone-marrow pathologies, like osteoporosis, bone tumors, and vertebral compression fractures are described.

title: Can pretreatment ADC values predict recurrence of bladder cancer after transurethral resection?
abstract: The aim of this retrospective study was to investigate the association between the pretreatment apparent diffusion coefficient (ADC) value and recurrence of bladder cancer after transurethral resection.



Patients with superficial bladder cancer were identified. Mean ADC values of the tumors were compared between patients with and without recurrence following trans-urethral resection. A receiver-operator characteristic curve was used for determining the optimal cutoff ADC value. Univariate and multivariate analyses were used to determine the effect of ADC values and other factors.



With a mean follow-up period of 25 months, bladder cancer recurred in 14 of 44 patients (32%). The mean ADC value of tumors in patients with recurrence was lower than in those without recurrence (1.08 mm2/s vs. ) mm2/s; p=0.003). The optimal cutoff ADC value for predicting recurrence was determined to be ) mm2/s. A modest and significant negative correlation was observed between the ADC values and tumor size (r=-0.436, p=0.008). After adjustment for size and risk groups, an ADC value equal to or less than the optimal cutoff remained a significant predictor of recurrence (odds ratio 6.3, 95% CI 1.23-32.2, p=0.027).



Pretreatment ADC values may be an independent predictor of bladder cancer recurrence.

title: High‐grade bladder cancer: Association of the apparent diffusion coefficient with metastatic disease: Preliminary results
abstract: To assess the utility of apparent diffusion coefficient (ADC) values obtained from diffusion‐weighted imaging (DWI) in distinguishing high‐grade bladder cancer with and without metastatic disease.

title: Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity to chemoradiotherapy in muscle-invasive bladder cancer.
abstract: In chemoradiation (CRT)-based bladder-sparing approaches for muscle invasive bladder cancer (MIBC), patients who respond favorably to induction CRT enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus, accurate prediction of CRT sensitivity would optimize patient selection for bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that quantifies the diffusion of water molecules in a noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of MIBC.



The study cohort consisted of 23 MIBC patients (cT2/T3 = 7/16) who underwent induction CRT consisting of radiotherapy to the small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days), followed by partial or radical cystectomy. All patients underwent DW-MRI before the initiation of treatment. Associations of apparent diffusion coefficient (ADC) values with CRT sensitivity were analyzed. The proliferative potential of MIBC was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic biopsy specimens.



Thirteen patients (57%) achieved pathologic complete response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC values (median, 0.63 × 10(-3) mm(2)/s; range, 0.43-0.77) than CRT-resistant (no pCR) MIBCs (median, 0.84 × 10(-3) mm(2)/s; range, 0.69-1.09; p = 0.0003). Multivariate analysis identified ADC value as the only significant and independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 ×10(-3) mm(2)/s increase, 1.03; 95% confidence interval, 1.01-1.08). With a cutoff ADC value at 0.74 × 10(-3) mm(2)/s, sensitivity/specificity/accuracy in predicting CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive MIBCs (p = 0.0005) and significantly and inversely correlated with ADC values (ρ = -0.67, p = 0.0007).



DW-MRI is a potential biomarker for predicting CRT sensitivity in MIBC. DW-MRI may be useful to optimize patient selection for CRT-based bladder-sparing approaches.

title: ErbB2 and NFκB Overexpression as Predictors of Chemoradiation Resistance and Putative Targets to Overcome Resistance in Muscle-Invasive Bladder Cancer
abstract: Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC.

title: p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer.
abstract: To determine whether p53, p21, pRB, and/or p16 expression is associated with bladder cancer stage, progression, and prognosis.



Immunohistochemical staining for p53, p21, pRB, and p16 was carried out on serial sections from archival specimens of 80 patients who underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer (median follow-up, 101 months).



p53, p21, and pRB or p16 expression was altered in 45 (56%), 39 (49%), and 43 (54%) tumors, respectively. Sixty-six patients (83%) had at least one marker altered, and 21 patients (26%) had all three altered. Abnormal expressions of p53, p21, and pRB/p16 expression were associated with muscle-invasive disease (P=.007, P=.003, and P=.003, respectively). The alteration of each marker was independently associated with disease progression (P< or =.038) and disease-specific survival (P< or =.039). In multivariable models that included standard pathologic features and p53 with p21 or p53 with pRB/p16, only p53 and lymph node metastases were associated with bladder cancer progression (P< or =.026) and death (P< or =.028). In models that included p21 and pRB/p16, only p21 and lymph node metastases were associated with bladder cancer progression (P< or =.022) and death (P< or =.028). In a model that included the combined variables p53/p21 and pRB/p16, only p53/p21 and lymph node status were associated with bladder cancer progression (P< or =.047) and death (P< or =.036). The incremental number of altered markers was independently associated with an increased risk of bladder cancer progression (P=.005) and mortality (P=.007).



Although altered expression of each of the four cell cycle regulators is associated with bladder cancer outcome in patients undergoing radical cystectomy, p53 is the strongest predictor, followed by p21, suggesting a more pivotal role of the p53/p21 pathway in bladder cancer progression.

title: HER2 overexpression in muscle‐invasive urothelial carcinoma of the bladder: Prognostic implications
abstract: The HER2 (c‐erbB‐2) receptor is overexpressed in a variety of human malignant tumors and, in breast carcinoma, has been identified as a target for anti‐HER2–directed therapy with the monoclonal antibody (MAb) trastuzumab. The aim of this retrospective study was to evaluate immunohistochemic HER2 expression in a large cohort of muscle‐invasive urothelial cell carcinomas of the urinary bladder and to compare the results to pathologic characteristics and survival. Paraffin‐embedded tumor specimens from 138 patients undergoing radical cystectomy for muscle‐invasive bladder carcinoma were studied immunohistochemically with the Food and Drug Administration (FDA)‐approved HercepTest (Dako, Glostrup, Denmark). HER2 overexpression was observed in 57 of 138 tumors (41%) and occurred more frequently in high‐grade carcinomas than in low‐grade carcinomas (p = 0.036). No significant relationship with HER2 overexpression was registered for tumor staging and lymph node status. Kaplan‐Meier curves showed a significantly worse disease‐related survival (p = 0.034) in patients with HER2‐overexpressing tumors compared to those without HER2 overexpression. In addition to lymph node status (p = 0.0001; relative risk [RR] = 2.93), HER2 status (p = 0.020; RR = 2.22) was identified as an independent predictor for disease‐related survival in a multivariate analysis. These results suggest that HER2 expression might provide additional prognostic information in patients with muscle‐invasive bladder carcinomas. Because many of these patients harbor HER2‐overexpressing tumors, clinical trials evaluating the efficacy of trastuzumab in bladder carcinoma are warranted.

title: Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy
abstract: Tested was whether the assessment of 5 established bladder cancer biomarkers (p53, pRB, p21, p27, and cyclin E1) could improve the ability to predict disease recurrence and cancer‐specific survival after radical cystectomy in patients with pTa‐3N0M0 urothelial carcinoma of the bladder (UCB).

title: Initial experience of diffusion-weighted magnetic resonance imaging to assess therapeutic response to induction chemoradiotherapy against muscle-invasive bladder cancer.
abstract: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DWI) in predicting therapeutic response to low-dose chemoradiotherapy (LCRT) against muscle-invasive bladder cancer (MIBC). Accurate assessment of response to induction therapy is an essential part of bladder-sparing therapeutic protocols against MIBC. However, conventional imaging studies are not useful in evaluating therapeutic response because of their inability to distinguish residual cancer from changes secondary to the treatment.



Twenty patients with clinical T2-4aN0M0 bladder urothelial carcinoma (T2/T3/T4a: n = 10/8/2) who underwent induction LCRT comprising external beam radiotherapy to the bladder (40 Gy) concomitant with 2 cycles of cisplatin administration (20 mg/d for 5 days) followed by partial (n = 13) or radical cystectomy (n = 7) were prospectively enrolled. The patients underwent magnetic resonance imaging examinations with T2-weighted imaging (T2W), dynamic contrast-enhanced T1-weighted imaging (DCE), and DWI after LCRT. A finding of each protocol was compared with a pathologic finding of cystectomy specimen.



Pathologic examination of cystectomy specimens revealed pathologic complete response in 13 (65%) of the 20 patients. The sensitivity/specificity/accuracy of T2W, DCE, and DWI in predicting pathologic response was 43/45/44%, 57/18/33%, and 57/92/80%, respectively. Despite comparable sensitivity, DWI was significantly superior in specificity and accuracy to T2W (P = .03 and .02, respectively) and DCE (P = .002 for both).



This is the first study to show the feasibility of DWI over T2W and DCE for assessing therapeutic response to induction chemoradiotherapy against MIBC. The high specificity of DWI indicates that DWI is useful to accurately predict pathologic complete response, allowing more optimal patient selection in bladder-sparing protocols.

title: Diffusion‐weighted magnetic resonance imaging in follow‐up of superficial urinary bladder carcinoma after transurethral resection: initial experience
abstract: Study Type – Diagnostic (exploratory cohort)