bluuebunny/crossref_metadata_2025 huggingface dataset:
Heavy Ion Therapy: Status and Perspectives
Authors: Jäkel O. , Schulz-Ertner D. , Karger C.P. , Nikoghosyan A. , Debus J.
Published: October 2014

Starting with the pioneering work at the University of California in Berkeley in 1977, heavy ion radiotherapy has been of increasing interest especially in Japan and Europe in the last decade. There are currently 3 facilities treating patients with carbon ions, two of them in Japan within a clinical setting. In Germany, a research therapy facility is in operation and the construction of a new hospital based facility at the Heidelberg university will be started soon. An outline of the current status of heavy ion radiotherapy is given with emphasis to the technical aspects of the respective facilities. This includes a description of passive and active beam shaping systems, as well as their implications for treatment planning and dosimetry. The clinical trials and routine treatments performed at the German heavy ion facility are summarized.

An overview over the upcoming new facilities and their technical possibilities is given. It is discussed what the necessary improvements are to fully exploit the potential of these facilities. Especially the new Heidelberg facility with the possibility of active beam scanning in combination with the first isocentric gantry for ions and offering beams of protons, helium, oxygen and carbon ions has implications on treatment planning, dosimetry and quality assurance. The necessary and ongoing developments in these areas are summarized. The new facilities also offer the possibilities to perform more extensive clinical studies and to explore future indications for radiotherapy with heavy ions. An overview over the indications and treatment schemes is also given.
The Increased Biological Effectiveness of Heavy Charged Particles: From Radiobiology to Treatment Planning
Authors: Krämer M. , Weyrather W. K. , Scholz M.
Published: October 2014

The increased biological effectiveness of heavy charged particle beams like e.g., carbon ions in the tumor volume in comparison to the lower effectiveness in the surrounding healthy tissue represents one of the major rationales for their application in tumor therapy. This increased effectiveness also characterizes the advantage of heavier ions compared to proton beams. The increased effectiveness has to be taken into account in treatment planning in order to estimate the corresponding photon equivalent doses in normal and tumor tissues, thus allowing a link e.g., to normal tissue dose limits in conventional photon therapy.

Due to the complex dependencies of RBE on parameters like dose, beam energy, LET, atomic number and cell or tissue type, the relevant RBEs cannot be solely determined from experimental data. Therefore, within the framework of the pilot project of tumor therapy with carbon ions performed at GSI Darmstadt, treatment planning is based on a biophysical model, which has been extensively tested.

The paper first summarizes the essential systematic dependencies of RBE on different parameters like e.g., dose, LET, atomic number and cell type. The basic principle of the biophysical model is then introduced, and special emphasis is given to the application of the model to in vivo and clinical endpoints. Model predictions are compared to experimental data in vitro and in vivo. Finally, the implementation of the biophysical model in the treatment planning procedure is presented. The biological verification of the whole treatment planning procedure is explained and examples of patient treatment plans are given.
Optimization of Beam Parameters and Treatment Planning for Intensity Modulated Proton Therapy
Authors: Trofimov Alexei , Bortfeld Thomas
Published: October 2014

One of the objectives of the ongoing research and development work at the Northeast Proton Therapy Center (NPTC) in Boston is to perform optimized intensity modulated proton therapy (IMPT) treatments. Such treatments may be delivered by magnetically scanning a narrow proton pencil beam across the target volume, while both the scanning speed and the intensity of the beam are modulated. Localization of the proton dose in space allows one to yield dose distributions that are highly conformal to the target volume, thus minimizing the dose delivered to the surrounding healthy tissue. The aim of the current research is to determine technically optimal and clinically relevant specifications for the scanned beam delivery system, which is being developed in collaboration with Ion Beam Applications (IBA); and to create a link between the treatment planning and the beam delivery. IMPT treatment planning is performed for patient cases treated at the NPTC, with KonRad Pro software developed at the German Cancer Research Center (DKFZ). For the IMPT delivery, the proton intensity maps, optimized for discrete pencil beam spots, need to be translated into continuous scanning patterns. At the same time it is necessary to minimize the discrepancy between the planned and delivered doses which may result from such conversion, as well as from the technical limitations of the delivery system. Possibilities have been investigated for improving the proton dose conformity by optimizing the beam and scanning nozzle parameters, and by taking the specifics and limitations of the system into account in the treatment planning stage.
Optical Systems for in Vivo Molecular Imaging of Cancer
Authors: Sokolov Konstantin , Aaron Jesse , Hsu Betsy , Nida Dawn , Gillenwater Ann , Follen Michele , MacAulay Calum , Adler-Storthz Karen , Korgel Brian , Descour Michael , Pasqualini Renata , Arap Wadih , Lam Wan , Richards-Kortum Rebecca
Published: October 2014

Progress toward a molecular characterization of cancer would have important clinical benefits; thus, there is an important need to image the molecular features of cancer in vivo. In this paper, we describe a comprehensive strategy to develop inexpensive, rugged and portable optical imaging systems for molecular imaging of cancer, which couples the development of optically active contrast agents with advances in functional genomics of cancer. We describe initial results obtained using optically active contrast agents to image the expression of three well known molecular signatures of neoplasia: including over expression of the epidermal growth factor receptor (EGFR), matrix metallo-proteases (MMPs), and oncoproteins associated with human papillomavirus (HPV) infection. At the same time, we are developing inexpensive, portable optical systems to image the morphologic and molecular signatures of neoplasia noninvasively in real time. These real-time, portable, inexpensive systems can provide tools to characterize the molecular features of cancer in vivo.
Investigating Sun-damaged Skin and Actinic Keratosis with Optical Coherence Tomography: A Pilot Study
Authors: Barton Jennifer K. , Gossage Kirk W. , Xu Wei , Ranger-Moore James R. , Saboda Kathylynn , Brooks Christine A. , Duckett Laura D. , Salasche Stuart J. , Warneke James A. , Alberts David S.
Published: October 2014

Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical manifestation in the multistep process of skin carcinogenesis to invasive squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts. Noninvasive measures of AK severity are needed to assess the efficacy of chemoprevention agents. We performed a pilot study on 20 participants to investigate the OCT appearance of sun-protected skin of the upper inner arm as well as sun-damaged skin and early AKs of the dorsal forearms, and to determine if features or quantitative measures in Optical Coherence Tomography (OCT) images could be used to reliably differentiate between these categories. OCT images of upper inner arm (normal appearing skin) showed skin layers and features (stratum corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally in this participant group the subcutaneous fat layer was usually identified. Sun-damaged skin was characterized by increased signal in the epidermis and rapid attenuation of light. AKs were diverse in appearance but frequently characterized by high surface reflection, the presence of a low-signal band in the stratum corneum, and heterogeneous appearance in the epidermis/dermis. Significant differences were found between skin categories using measures of stratum corneum and epidermal/dermal depths and intensities. The presence of a dark band in the stratum corneum was 79% sensitive and 100% specific for AK. This study indicates that OCT holds promise as a useful technique for identifying and characterizing AKs and monitoring their response to chemoprevention agents.
An Operational Near-Infrared Fluorescence Imaging System Prototype for Large Animal Surgery
Authors: De Grand Alec M. , Frangioni John V.
Published: October 2014

Near-infrared (NIR) fluorescence imaging has the potential to revolutionize human cancer surgery by providing sensitive, specific, and real-time intraoperative visualization of normal and disease processes. We have previously introduced the concept of a low-cost, safe, and easy-to-use NIR fluorescence imaging system that permits the surgeon to “see” surgical anatomy and NIR fluorescence simultaneously, non-invasively, with high spatial resolution, in real-time, and without moving parts [Nakayama et al. Molecular Imaging 1, 365–377 (2002)]. In this study, we present an operational prototype designed specifically for use during large animal surgery. Such a system serves as a foundation for future clinical studies. We discuss technical considerations, and provide details of the implementation of subsystems related to excitation light, light collection, computer, and software. Using the prototype, and the clinically available NIR fluorophore indocyanine green, we demonstrate vascular imaging in 35 kg pigs. Cancer-specific applications of this imaging system include image-guided cancer resection with real-time assessment of surgical margins, image-guided sentinel lymph node mapping, intraoperative mapping of tumor and normal vasculature, image-guided avoidance of critical structures such as nerves, and intraoperative detection of occult metastases in the surgical field. Taken together, this study describes an optical imaging system engineered for eventual translation to the clinic.
Enhanced Surface Registration Techniques for Patient Positioning Control in Breast Cancer Radiotherapy
Authors: Riboldi M. , Baroni G. , Orecchia R. , Pedotti A.
Published: October 2014

Experimental data, describing patient inter-fractional set-up errors in the clinical practice of breast radiotherapy, were exploited to simulate the performance in errors detection and correction of a constrained surface registration procedure, based on a hybrid configuration of control points (passive and laser). During 47 treatment sessions in three patients undergoing post-quadrantectomy radiotherapy, an opto-electronic localizer was used to acquire the three-dimensional coordinates of the hybrid control points, being two passive markers placed on selected skin landmarks on the sternum. Laser scanning technique was also applied for the acquisition of the 3-D surface model of the irradiated body area, which was used as reference for the automatic position correction procedure. A constrained surface registration algorithm was applied to estimate the rigid spatial transformation, describing the local errors affecting the control points. The improvement of the irradiation geometrical setup, by correcting the patient position according to the estimated spatial transformation parameters, was simulated. Results showed that the proposed surface registration method allowed us to detect and significantly (Wilcoxon signed rank analysis) reduce the initial misalignments, which exhibited overall median and 75th percentile values equal to 4.26 mm and 5.76 mm. Simulated residual errors dropped down to median and 75th percentile values measuring 2.95 mm and 3.87 mm, respectively. These results confirmed the high potentiality of surface registration techniques for the opto-electronic automatic patient positioning control in breast cancer radiotherapy.
Cryosurgery for Lung Cancer: Clinical Results and Technical Aspects
Authors: Maiwand M. O. , Asimakopoulos G.
Published: October 2014

Lung carcinoma is the most frequently diagnosed malignancy in the world, with the incidence increasing through the 20th century. Presentation may be as a tumor mass primarily obstructing the central bronchial lumen, or a mass infiltrating lung tissue. Cryosurgery can be used as a method of palliative treatment for both these endobronchial and extra-bronchial presentations. The aim of this study is two-fold: to present data relating to our extensive experience in treating obstructing endobronchial tumors and to present our initial results of direct cryosurgery to infiltrating lung tumor masses.

During a nine-year period, 521 consecutive patients (male:female ratio 1.8:1) with a mean age of 67.9 years who had advanced obstructive tracheobronchial malignant tumors underwent cryosurgery with a mean of 2.4 treatments per patient. Hemoptysis, cough, dyspnoea and chest pain improved by at least one class in 76.4%, 69.0%, 59.25% and 42.6% (p<0.01) of symptomatic patients respectively. Quality of life studies showed that the mean Karnofsky score improved from 60 ± 7 to 75 ± 8 and the mean WHO score from 3.04 ± 0.7 to 2.20 ± 0.56. There were 7 (1.2%) in-hospital deaths, and 2-year survival was 15.9%.

Direct cryosurgery to carcinoma of the lung was performed on 15 patients at exploratory thoracotomy. Results showed an increase in FEV1 from 1.80 ± 0.6 liters to 1.95 ± 0.8 (8.3%) liters and in FVC from 2.50 ± 0.8 to 2.68 ± 0.8 liters (7.2%). The Karnofsky score improved from 68 ± 9 to 78 ± 10 and the WHO score from 2.63 ± 0.81 to 2.38 ± 0.78 (9.6%). Major symptoms including cough, dyspnoea, and hemoptysis were assessed and showed improvement in 77.8%, 66.7%, and 100% (p<0.01) of symptomatic patients respectively.

Patients were followed for a mean period of 18 months (range 4–84 months). Median survival from the date of surgery (Kaplan-Meier, 95%Cl) was 11.6 (6.8 to 18.2) months, range 1 to 84 months.

Cryosurgery provides a safe and effective method for the palliation of advanced central bronchial obstructive tumors, and compares favorably with other methods in terms of safety, cost, and complications. Initial experience suggests that similar palliation may be achieved by cryosurgery applied to advanced parenchymal tumor masses.
Cryosurgery of the Adrenal Gland
Authors: Munver Ravi , Sosa R. Ernest
Published: October 2014

Adrenalectomy has become the standard of care for the management of hormonally active adrenal masses. Minimally invasive adrenal-sparing surgical techniques have recently been introduced for the treatment of benign adrenal lesions, with the intent of complete excision or destruction. Cryosurgery is one such modality that is focused on reducing patient morbidity and hastening postoperative recovery, while preserving normal tissue. The emerging interest in cryosurgery is attributable to improved delivery systems and advances in radiologic imaging. However, questions remain about the risks and benefits of this technology for adrenal-sparing surgery in terms of safety and effective tissue destruction. We examine our experience and discuss our results with open and laparoscopic adrenal cryosurgery.
Image Guided I125 Prostate Brachytherapy with Hybrid Interactive Mick Technique in the Community Setting: How Does it Compare?
Authors: Shanahan Thomas G. , Mueller Paul W. , Roszhart David A. , Severino William C. , Bhate Amit D. , Nanavati Parashar J. , Madison James B. , Dixon Eugene J. , Ost Loren B. , Strode Lorraine L. , Wands Naomi S. , Maxey Randy B.
Published: October 2014

The aim of this study is to evaluate the target coverage, procedural techniques, and merits of Hybrid Interactive Mick (HIM) I125 transperineal permanent implantation (TPPI) of the prostate performed with 10 urologists in a community hospital. Detailed day 0 post-implant dosimetric evaluations of TPPI procedures were performed on 333 consecutive monotherapy patients treated between September 2000 and November 2003 at a single institution. All patients underwent TPPI with HIM. Pelvic and CXR films were obtained for a manual seed count at day 0 and again > day 90 on 175 patients. The HIM-prostate brachytherapy performed in a community hospital provided median D 90, V100, and V150 values of 157Gy, 94%, and 42.3%, respectively. 18% of patients had seed migration to the lungs while 2% had seed migration to the bladder. Only 7 patients (4%) had 2 or more seeds migrate to the lungs. Procedure times average 38 minutes and number of needles used averaged 18. The post-implant urinary retention rate was 2.1% Use of HIM-prostate brachytherapy in the community setting with multiple urologists reproducibly maintained excellent and consistent dosimetric coverage. Procedure times and number of needles used were minimized, and with careful attention to image-guided technique, seed migration to bladder and lung was also minimized.
Proton Radiation and TNF-α/Bax Gene Therapy for Orthotopic C6 Brain Tumor in Wistar Rats
Authors: Gridley Daila S. , Miller Glen M. , Luo Xian , Cao Jeffrey D. , Timiryasova Tatyana M. , Fodor Istvan , Slater James M.
Published: October 2014

High-grade tumors of the brain remain virtually incurable with current therapeutic regimens, new approaches to augment existing therapies need to be explored. The major goal of this pilot study was to evaluate the feasibility of gene therapy using plasmid DNA encoding tumor necrosis factor-α and bax together with proton radiation in an immunocompetent animal model with orthotopic brain tumor. C6 glioma cells were stereotactically implanted into the left hemibrain of Wistar rats (day 0). On day 5, the appropriate groups received intratumoral pGL1-TNF-α and pGL1-Bax (10 μg each), parental plasmid pWS4 (20 μg), or PBS. Hemibrain proton irradiation (10 Gy, 90 MeV, single fraction) was delivered 18–20 hr later. Rats were euthanized when signs of illness appeared. In addition, a subset of animals from each group was euthanized on day 9 for immune and other assays. By day 9, 25%, 20%, and 10% of rats treated with PBS, pWS4, or pGL1-TNF-μ/pGL1-Bax, respectively, had been euthanized due to weight loss or other signs of illness, whereas all rats treated with pGL1-TNF-μ/pGL1-Bax + radiation or radiation alone were healthy (P<0.05). At this same time, the pGL1-TNF-μ/pGL1-Bax + radiation group had significantly elevated lymphocyte percentages (P<0.005 or less) and a relatively high level of lymphocytic infiltrate within tumors. Although the rats treated with pGL1-TNF-μ/pGL1-Bax had the highest levels of activated T helper (CD4+/CD71+) and T cytotoxic (CD8+/CD71+) cells, the values were not significantly different compared to the pWS4-injected control group. Splenocytes in all tumor cell-injected groups had higher mean values for DNA and protein synthesis compared to the non-tumor cell injected control group, whereas oxygen radical production by phagocytes was consistently higher in groups injected with plasmid or treated with radiation. Body, hemibrain, and spleen masses, white blood cell, red blood cell and platelet counts, hemoglobin, hematocrit, and transforming growth factor-β1 levels in plasma were similar among groups. The results demonstrate that treatment with pGL1-TNF-α/pGL1-Bax combined with proton hemibrain irradiation is safe under the conditions used. Overall, these data support further investigation of this unique combination therapy.
The Impact of Mid-Treatment MRI on Defining Boost Volumes in the Radiation Treatment of Glioblastoma Multiforme
Authors: Manon Rafael , Hui Susanta , Chinnaiyan Prakash , Suh John , Chang Eric , Timmerman Robert , Phan See , Das Rupak , Mehta Minesh
Published: October 2014

Radiation therapy is a central modality in the treatment of glioblastoma multiforme (GBM). Integral to adequate radiation therapy delivery is the appropriate determination of tumor volume and extent at the time treatment is being delivered. As a matter of routine practice, radiation therapy treatment fields are designed based on tumor volumes evident on preoperative or immediate post-operative MRIs; another MRI is generally not obtained for planning boost fields. In some instances the time interval from surgery to radiotherapy initiation is up to 5 weeks and the boost or “cone-down phase” commences 4–5 weeks later. The contrast enhanced T1 MRI may not be a totally reliable indicator of active tumor, especially in regions where such blood-brain barrier breakdown has not occurred. Moreover, these volumes may change during the course of treatment. This may lead to a geographic miss when mid-treatment boost volumes are designed based on a pre-radiotherapy MRI. The goal of this study is to examine how a mid-treatment MRI impacts the delineation and definition of the boost volume in GBM patients in comparison to the pre-treatment MRI scan, particularly when the tumor-specific agent Motexafin-Gadolinium is used.
Detectors for Digital Mammography
Authors: Yaffe Martin J. , Mainprize James G.
Published: October 2014

Interest in digital radiography was stimulated by the enthusiastic acceptance of computed tomography in the early 1970s. It quickly became apparent to the medical community that images with improved information content, whose display characteristics could be manipulated by the viewer, provided many advantages. Subsequently, digital systems for subtraction angiography and later for conventional projection radiography and fluoroscopy were developed. The timing of the introduction of these systems was highly dependent on the readiness of certain key component technologies to meet the requirements of each of these applications. These components are the x-ray detectors, analog to digital converters, computers, data storage systems, high-resolution electronic displays, and printers used in image acquisition, storage, and display. Mammography represents one of the most demanding radiographic applications, simultaneously requiring excellent contrast sensitivity, high spatial resolution, and wide dynamic range at as low of a radiation dose to the breast as is reasonably achievable while meeting the other requirements. For this reason, it is one of the last radiographic procedures to “go digital.” Here, some of the considerations related to the detector technology for digital mammography will be discussed and systems currently available will be described.
Combination of Digital Mammography with Semi-automated 3D Breast Ultrasound
Authors: Kapur Ajay , Carson Paul L. , Eberhard Jeffrey , Goodsitt Mitchell M. , Thomenius Kai , Lokhandwalla Murtuza , Buckley Donald , Roubidoux Marilyn A. , Helvie Mark A. , Booi Rebecca C. , LeCarpentier Gerald L. , Erkamp Ramon Q. , Chan Heang-Ping , Fowlkes J. Brian , Thomas Jerry A. , Landberg Cynthia E.
Published: October 2014

This paper describes work aimed at combining 3D ultrasound with full-field digital mammography via a semi-automatic prototype ultrasound scanning mechanism attached to the digital mammography system gantry. Initial efforts to obtain high x-ray and ultrasound image quality through a compression paddle are proving successful. Registration between the x-ray mammogram and ultrasound image volumes is quite promising when the breast is stably compressed. This prototype system takes advantage of many synergies between the co-registered digital mammography and pulse-echo ultrasound image data used for breast cancer detection and diagnosis. In addition, innovative combinations of advanced US and X-ray applications are being implemented and tested along with the basic modes. The basic and advanced applications are those that should provide relatively independent information about the breast tissues. Advanced applications include x-ray tomosynthesis, for 3D delineation of mammographic structures, and non-linear elasticity and 3D color flow imaging by ultrasound, for mechanical and physiological information unavailable from conventional, non-contrast x-ray and ultrasound imaging.
The Impact of Technological Advances on the Evolution of 3D Conformal Brachytherapy for Early Prostate Cancer
Authors: Nori Dattatreyudu , Reddy Nandanuri M. S. , Vaughan E. Darracott , Shemtov M. Mendel
Published: October 2014

Permanent implantation of I-125 and Pd-103 seeds is one of the widely used treatment options for the early stage prostate cancer with minimum normal tissue complications and long-term local control of the tumor. This is possible because of several technological advances made in the past decade to better understand the procedural aspects of implantations with the desired clinical outcome and with acceptable morbidities. In addition, with the widespread use of PSA testing, more widely disseminated information about prostate cancer and increased patient awareness, over 70% of patients are diagnosed early with localized disease and therefore are candidates for definitive local therapy. Delineation of soft tissue structures including the prostate, rectum, urethra and bladder has become more accurate with the use of imaging modalities including Ultrasound and MRI, with or without the CT. A re-evaluation of the dosimetric parameters of the radioactive sources has lead to a more precise estimate of the dose delivered to the prostate and the associated critical normal structures. Technological improvements in the post implant dosimetry have helped to understand the factors, which makes an implant a “good implant” or a “poor implant”. Intraoperative treatment planning with on line dosimetry is emerging as one of the best approaches for prostate brachytherapy. In addition, better software is now available producing dose-volume histograms with 3D target and normal tissue reconstruction. The combination of seed implant followed by IMRT would provide scope for differentially boosting the regions under-dosed because of uncontrollable and unexpected reasons during the implant and unsuspected micro extensions of the tumor.
The Male Lumpectomy: Rationale for a Cancer Targeted Approach for Prostate Cryoablation. A Review
Authors: Onik Gary
Published: October 2014

Lumpectomy to treat breast cancer has revolutionized the management of that disease. Lumpectomy showed that the quality of life of the individual patient can successfully be integrated into the equation of cancer treatment, without major loss of cancer treatment efficacy. Prostate cancer raises many of the same issues that breast cancer does in women. Impotence and incontinence, affects the male self image and psyche no less than the loss of a breast does a woman. Management of prostate cancer ranges from no treatment at all (“watchful waiting”) to treatments in which the whole gland is destroyed (radiation therapy, cryosurgery) or removed (radical prostatectomy), with presently no treatment in between these extremes. Pathologic literature indicates, however, that 35% of prostate cancers are solitary and unilateral. In addition, long term studies have confirmed that cryoabltion for prostate cancer is an efficacious treatment. In this paper we will examine the rationale for a “male lumpectomy” using cryoablation and present preliminary data supporting it's role in prostate cancer management.
Lighting up Tumors with Receptor-Specific Optical Molecular Probes
Authors: Achilefu Samuel
Published: October 2014

Accurate and rapid detection of tumors is of great importance for interrogating the molecular basis of cancer pathogenesis, preventing the onset of complications, and implementing a tailored therapeutic regimen. In this era of molecular medicine, molecular probes that respond to, or target molecular processes are indispensable. Although numerous imaging modalities have been developed for visualizing pathologic conditions, the high sensitivity and relatively innocuous low energy radiation of optical imaging method makes it attractive for molecular imaging. While many human diseases have been studied successfully by using intrinsic optical properties of normal and pathologic tissues, molecular imaging of the expression of aberrant genes, proteins, and other pathophysiologic processes would be enhanced by the use of highly specific exogenous molecular beacons. This review focuses on the development of receptor-specific molecular probes for optical imaging of tumors. Particularly, bioconjugates of probes that absorb and fluoresce in the near infrared wavelengths between 750 and 900 nm will be reviewed.
Computerized Detection of Mass Lesions in Digital Breast Tomosynthesis Images Using Two- and Three Dimensional Radial Gradient Index Segmentation
Authors: Reiser I. , Nishikawa R. M. , Giger M. L. , Wu T. , Rafferty E. , Moore R. H. , Kopans D. B.
Published: October 2014

Initial results for a computerized mass lesion detection scheme for digital breast tomosynthesis (DBT) images are presented. The algorithm uses a radial gradient index feature for the initial lesion detection and for segmentation of lesion candidates. A set of features is extracted for each segmented partition. Performance of two- and three dimensional features was compared. For gradient features, the additional dimension provided no improvement in classification performance. For shape features, classification using 3D features was improved compared to the 2D equivalent features. The preliminary overall performance was 76% sensitivity at 11 false positives per exam, estimated based on DBT image data of 21 masses. A larger database will allow for further development and improvement in our computer aided detection scheme.
The Use of Gene Therapy in Cancer Research and Treatment
Authors: Shinohara Eric T. , Lu Bo , Hallahan Dennis E.
Published: October 2014

Gene therapy involves identifying a gene of interest and then manipulating the expression of this gene through a variety of techniques. Here we specifically address gene therapy's role in cancer research. This paper will encompass thoroughly investigated techniques such as cancer vaccines and suicide gene therapy and the latest advancements in and applications of these techniques. It will also cover newer techniques such as Antisense Oligonucleotides and small interfering RNAs and how these technologies are being developed and used. The use of gene therapy continues to expand in cancer research and has an integral role in the advancement of cancer treatment.
Multiparametric and Multinuclear Magnetic Resonance Imaging of Human Breast Cancer: Current Applications
Authors: Jacobs Michael A. , Ouwerkerk Ronald , Wolff Antonio C. , Stearns Vered , Bottomley Paul A. , Barker Peter B. , Argani Pedram , Khouri Nagi , Davidson Nancy E. , Bhujwalla Zaver M. , Bluemke David A.
Published: October 2014

The exploration of novel imaging methods that have the potential to improve specificity for the identification of malignancy is still critically needed in breast imaging. Changes in physiologic alterations of soft tissue water associated with breast cancer can be visualized by magnetic resonance (MR) imaging. However, it is unlikely that a single MR parameter can characterize the complexity of breast tissue. Techniques such as multiparametric MR imaging, proton magnetic resonance spectroscopic (MRSI) imaging, and 23Na sodium MR imaging when used in combination provide a comprehensive data set with potentially more power to diagnose breast disease than any single measure alone. A combination of MR, MRSI, and 23Na sodium MR parameters may be examined in a single MR imaging examination, potentially resulting in improved specificity for radiologic evaluation of malignancy.
The Role of Diffusion Tensor Imaging in Establishing the Proximity of Tumor Borders to Functional Brain Systems: Implications for Preoperative Risk Assessments and Postoperative Outcomes
Authors: Ulmer John L. , Salvan Carmen V. , Mueller Wade M. , Krouwer Hendrikus G. , Stroe Georgetta O. , Aralasmak Ayse , Prost Robert W.
Published: October 2014

Diffusion Tensor Imaging (DTI) is a new MRI imaging technique sensitive to directional movements of water molecules, induced by tissue barriers. This provides a new form of contrast that allows the identification of functional white matter tracts within the brain, and has been proposed as a technique suitable for presurgical planning in brain tumor patients. Resection of primary brain tumors improves survival, functional performance, and the effectiveness of adjuvant therapies, provided that surgically-induced neurological deficits can be avoided. Diffusion Tensor Imaging (DTI) has the potential to establish spatial relationships between eloquent white matter and tumor borders, provide information essential to preoperative planning, and improve the accuracy of surgical risk assessments preoperatively. We present our experience in a series of 28 brain tumor patients where the integration of functional magnetic resonance imaging (fMRI) and DTI data was used to determine key anatomic spatial relationships preoperatively. Twice as many functional systems were localized to within 5 mm of tumor borders when DTI and fMRI were utilized for preoperative planning, compared to that afforded by fMRI alone. Our results show that the combined use of fMRI and DTI can provide a better estimation of the proximity of tumor borders to eloquent brain systems sub-serving language, speech, vision, motor and premotor functions. Additionally, a low regional complication rate (4%) observed in our series suggests that preoperative planning with these combined techniques may improve surgical outcomes compared to that previously reported in the literature. Larger studies specifically designed to establish the accuracy and predictive value of DTI in brain tumor patients are warranted to substantiate our preliminary observations.
Abnormal Vessel Tortuosity as a Marker of Treatment Response of Malignant Gliomas: Preliminary Report
Authors: Bullitt Elizabeth , Ewend Matthew G. , Aylward Stephen , Lin Weili , Gerig Guido , Joshi Sarang , Jung Inkyung , Muller Keith , Smith J. Keith
Published: October 2014

Despite multiple advances in medical imaging, noninvasive monitoring of therapeutic efficacy for malignant gliomas remains problematic. An underutilized observation is that malignancy induces characteristic abnormalities of vessel shape. These characteristic shape abnormalities affect both capillaries and much larger vessels in the tumor vicinity, involve larger vessels prior to sprout formation, and are generally not present in hypervascular benign tumors. Vessel shape abnormalities associated with malignancy thus may appear independently of increase in vessel density. We hypothesize that an automated, computerized analysis of vessel shape as defined from high-resolution MRA can provide valuable information about tumor activity during the treatment of malignant gliomas. This report describes vessel shape properties in 10 malignant gliomas prior to treatment, in 2 patients in remission during treatment, and in 2 patients with recurrent disease. One subject was scanned multiple times. The method involves an automated, statistical analysis of vessel shape within a region of interest for each tumor, normalized by the values obtained from the vessels within the same region of interest of 34 healthy subjects. Results indicate that untreated tumors display statistically significant vessel tortuosity abnormalities. These abnormalities involve vessels not only within the tumor margins as defined from MR but also vessels in the surrounding tissue. The abnormalities resolve during effective treatment and recur with tumor recurrence. We conclude that vessel shape analysis could provide an important means of assessing tumor activity.
Correlation of MR Perfusion Imaging and Vessel Tortuosity Parameters in Assessment of Intracranial Neoplasms
Authors: Parikh Anup H. , Smith J. Keith , Ewend Matthew G. , Bullitt Elizabeth
Published: October 2014

Advances in noninvasive imaging techniques such as magnetic resonance perfusion imaging have been found useful in grading cerebral neoplasms and have potential for significant clinical benefit. The purpose of this study was to determine the correlation between tumor vessel tortuosity as measured from vessels extracted from magnetic resonance angiograms (MRA) and perfusion parameters of cerebral blood flow (CBF) and cerebral blood volume (CBV) in intracranial neoplasms. We hypothesized that tumor blood vessel tortuosity measures and perfusion measures would be correlated, since both are increased by tumor angiogenesis. 18 patients with 19 cerebral neoplasms were evaluated with conventional MR imaging and dynamic contrast-enhanced T2-weighted perfusion MR imaging (PWI). Both benign and malignant lesions were included, as were hyper- and hypovascular tumors. Regions of interest were plotted within the tumor area to locate foci of maximum CBV and CBF. CBV and CBF measurements were also recorded in contralateral normal appearing white matter to calculate relative CBV (rCBV) and relative CBF (rCBF). Vessel tortuosity analyses were conducted upon vessels segmented from MRA images of the same patients using two tortuosity descriptors (SOAM and ICM), which have previously been demonstrated to have efficacy in separating benign from malignant disease. Linear regression analyses were conducted to determine if correlations exist between CBV or CBF and the two tortuosity measurements. For the overall set of tumors, no significant correlations were found between flow or volume measures and the tortuosity measures. However, when the 7 glioblastoma multiforme tumors were examined as a subgroup, the following significant correlations were found: rCBV and SOAM (R2=0.799), rCBV and ICM (R2=0.214). Our results demonstrate that MR perfusion imaging data do not correlate significantly with vessel tortuosity parameters as determined from the larger vessels seen by MRA. However, for subgroups of a particular tumor type such as GBM, there may be significant correlations. It appears that perfusion and tortuosity data may provide independently useful data in the assessment of cerebral neoplasms.
Geomatics for Precise 3D Breast Imaging
Authors: Alto Hilary
Published: October 2014

Canadian women have a one in nine chance of developing breast cancer during their lifetime. Mammography is the most common imaging technology used for breast cancer detection in its earliest stages through screening programs. Clusters of microcalcifications are primary indicators of breast cancer; the shape, size and number may be used to determine whether they are malignant or benign. However, overlapping images of calcifications on a mammogram hinder the classification of the shape and size of each calcification and a misdiagnosis may occur resulting in either an unnecessary biopsy being performed or a necessary biopsy not being performed. The introduction of 3D imaging techniques such as standard photogrammetry may increase the confidence of the radiologist when making his/her diagnosis.

In this paper, traditional analytical photogrammetric techniques for the 3D mathematical reconstruction of microcalcifications are presented. The techniques are applied to a specially designed and constructed x-ray transparent Plexiglas phantom (control object). The phantom was embedded with 1.0 mm x-ray opaque lead pellets configured to represent overlapping microcalcifications. Control points on the phantom were determined by standard survey methods and hand measurements. X-ray films were obtained using a LORAD M-III mammography machine.

The photogrammetric techniques of relative and absolute orientation were applied to the 2D mammographic films to analytically generate a 3D depth map with an overall accuracy of 0.6 mm. A Bundle Adjustment and the Direct Linear Transform were used to confirm the results.
Value of Electrical Impedance Scanning (EIS) in the Evaluation of BI-RADS™ III/IV/V-Lesions
Authors: Diebold Thomas , Jacobi Volkmar , Scholz Bernhard , Hensel Conny , Solbach Christine , Kaufmann Manfred , Viana Fernando , Balzer Joern , Peters Jutta , Vogl Thomas
Published: October 2014

Two hundred and fifty-six (256) patients (72% preoperative, 28% pre-Mammotome) were prospectively examined with EIS using the TS 2000 (TransScan Research and Development Center, Israel; temporarily distributed by Siemens, Erlangen) with the “LOS”-software (level of suspicion). All exams were performed with the targeted scan probe, the observer knowing all clinical and imaging facts. The area of the lesions was examined with EIS at least with 5 single scans. The evaluation included a scaling of lesions from 1 (surely benign) up to 5 (highly suggestive for malignancy) as well as the additional notification of spots. Results of EIS were based upon the automatic scaling which is provided by the software and were compared with mammography and histology. Furthermore the influence of the histology, size of lesions, and presence/absence of spots on the EIS results were analyzed.

Histology revealed benign results in 138 lesions and malignant results in 118 lesions (DCIS=61, ID-Ca=51, IL-Ca=5, mucinous Ca=1). Mammography as expected yielded high values with 91% sensitivity and 62% specificity. Overall sensitivity of EIS was 75.4%, specificity 42.03%, negative predictive value 66.7% and positive predictive value 52.7% (89 TP, 58 TN, 80 FP, 29 FN). EIS was false negative in 20 ID-Ca, 3 IL-Ca, 1 IDL-Ca, 4 DCIS, and 1 mucinous carcinoma. Sensitivity and specificity of EIS did not differ for the different histological differentiations neither for the degree of invasion. Also the additional notification of “spots” didn't show a correlation to malignancy. There were significant differences of the sensitivity of EIS regarding the tumor size. While EIS correctly diagnosed 85% of lesions <10 mm in size, only 64% of lesions >10 mm were detected. Most frequent lesion types for false positives were mastopathy (55/80 FP) and fibroadenoma (21/80 FP). Patient acceptance of EIS was perfect and there were no drop outs because of movement artifacts.

In conclusion the “LOS”-software clearly improved the clinical performance of the TS 2000 as compared to the initial software. The high sensitivity of EIS in small cancers which was found in our study may indicate an advantage of this method. However, the overall sensitivity and specificity with this setup of EIS is still far too low. Further improvements especially including the measurement of higher frequencies should be realized.
Performance Evaluation of Image Processing Algorithms in CADe
Authors: Wirth Michael A.
Published: October 2014

One of the key limitations of existing image processing algorithms for computer-aided detection (CADe) is that they are often designed and evaluated in an ad hoc manner.

This paper characterizes some of the issues and shortcomings in existing performance evaluation paradigms for image processing algorithms in breast cancer screening, particularly in the context of computer aided detection. We present the framework for establishing a performance evaluation process using standardized criteria. We conclude with some specific recommendations to improve the infrastructure for evaluation the performance of image processing algorithms.
Novel use of Single X-Ray Absorptiometry for Measuring Breast Density
Authors: Shepherd John A. , Herve Lionel , Landau Jessie , Fan Bo , Kerlikowske Karla , Cummings Steve R.
Published: October 2014

Breast density is one of the strongest known breast cancer risk factors. Breast density has primarily been measured by either categorical scores of the proportion of opacity on a screening mammogram or as a ratio of the delineated dense area to the total breast area on a mammogram. These methods are limited by their subjectivity, their lack of absolute reference standards, and lack of automation for clinical use.

We present a novel automated method for measuring breast composition we call Breast Compositional Density measured using single X-ray absorptiometry techniques, or BDSXA. BDSXA measures breast compositional density by comparing the opacity on the mammogram to two reference standards imaged with each breast. We present the mathematical derivation of BDSXA, methods for correcting for radiographic nonuniformity in the mammogram, and in vitro measures of accuracy and repeatability. Using phantoms, BDSXA has been shown to have a long-term repeatability of better than 2% for a breast composition range of 0 to 100% fibroglandular density.
Radiation-enhanced Endostatin Gene Expression and Effects of Combination Treatment
Authors: Luo Xian , Andres Melba L. , Timiryasova Tatyana M. , Fodor Istvan , Slater James M. , Gridley Daila S.
Published: October 2014

Targeting cells that support tumor growth by administering potent angiogenesis inhibitors is currently an area of intense interest. In the present study, a unique plasmid vector for the mouse endostatin gene, pXLG-mEndo, was constructed and evaluated with and without radiation using the Lewis lung carcinoma (LLC) cell line. The physical properties of the expressed endostatin protein were validated by PCR, gel electrophoresis, and Western blot. Enzyme-linked immunosorbent and immunocytochemical analyses for the therapeutic gene demonstrated that transfected LLC cells secreted the protein into the medium. Exposure of the cells to 2 gray (Gy) γ-rays reduced the time to reach the maximum expression level of the endostatin gene and also increased the amount of secreted endostatin protein (P<0.001). Biological activity of the endostatin was demonstrated by the inhibition of tube formation by human umbilical vein endothelial cells (HUVEC). Based on 3 H-thymidine incorporation, endostatin expression significantly depressed DNA synthesis in HUVEC and LLC cells compared to controls transfected with parental vector or no vector (P>0.005). In addition, radiation increased the efficiency of endostatin-mediated inhibition of both cell types over a 3-day period post-exposure (P<0.05 or less). Intratumoral injection of 100 μg pXLG-mEndo combined with 10 Gy radiation significantly delayed LLC tumor growth, especially when each modality was delivered twice (P<0.05 or less compared to all other groups). No toxicity was observed. These findings are very promising and suggest that endostatin therapy with a plasmid vector, such as pXLG-mEndo, may enhance the efficacy of radiotherapy for lung cancer.