bluuebunny/crossref_metadata_2025 huggingface dataset:
Preclinical ex vivo expansion of G‐CSF‐mobilized peripheral blood stem cells: effects of serum‐free media, cytokine combinations and chemotherapy
Authors: Li Karen , Li Chi Kong , Chuen Carmen Ka Yee , Tsang Kam Sze , Fok Tai Fai , James Anthony Edward , Lee Shuk Man , Shing Matthew Ming Kong , Chik Kai Wai , Yuen Patrick Man Pan
Published: January 2005

Abstract:  Objectives: Ex vivo expansion of granulocyte‐colony stimulating factor (G‐CSF)‐mobilized peripheral blood stem cells (PBSC) is a promising approach for overcoming the developmental delay of bone marrow (BM) reconstitution after transplantation. This project investigated the effects of culture duration, serum‐free media, cytokine combinations, and chemotherapy on the outcomes of expansion. Methods: Enriched CD34+ cells were cultured for 8 or 10 d in serum‐free media (QBSF‐60 or X‐Vivo 10) and four combinations of cytokines consisting of recombinant human pegylated‐megakaryocyte growth and development factor, stem cell factor, flt‐3 ligand, G‐CSF, interleukin (IL)‐6, platelet‐derived growth factor (PDGF), and IL‐1β. Results: Eight days of culture in QBSF‐60 significantly supported efficient expansions of CD34+ cells, CD34+ CD38− cells, colony‐forming units (CFU) of myeloid, erythroid, megakaryocytic, and mixed lineages to 3.76‐, 14.4‐, 28.3‐, 24.0‐, 38.1‐, and 15.7‐fold, respectively. Whilst PDGF or IL‐6 enhanced the expansion of early, myeloid, and erythroid progenitors, IL‐1β specifically promoted the megakaryocytic lineage. Engraftment of human CD45+ cells were detectable in all non‐obese diabetic/severe‐combined immunodeficient mice transplanted with expanded PBSC from donor samples, being 5.80 ± 3.34% of mouse BM cells. The expansion and engraftment capacity of CD34+ cells from subjects postchemotherapy were significantly compromised across the panel of progenitor cells. Conclusion: Our results provided an optimized protocol for PBSC expansion, applicable to ameliorating neutropenia and thrombocytopenia in post‐BM transplant patients by the prompt provision of progenitor cells. For postchemotherapy patients, expansion products might provide committed progenitors for improving short‐term engraftment, but not self‐renewable stem cells.
Serum IgM, IgG and IgA block by F(ab′)2‐dependent mechanism the binding of natural IgG autoantibodies from therapeutic immunoglobulin preparations to self‐antigens
Authors: Djoumerska Iglika K. , Tchorbanov Andrey I. , Donkova‐Petrini Vladimira D. , Pashov Anastas D. , Vassilev Tchavdar L.
Published: January 2005

Abstract:  Natural polyreactive IgG autoantibodies are present in the plasma of healthy individuals and as a result in pooled therapeutic intravenous immunoglobulin (IVIg) preparations. The spectrum of self‐antigens to which these autoantibodies bind, their fate after intravenous infusion and their biological activity are not well understood. The identity of serum proteins that mask binding of natural autoantibodies to self‐proteins is a matter of controversy. The spectrum of native serum proteins bound by IVIg was analyzed by two‐dimensional electrophoresis. The reactivity of IVIg was directed mainly to circulating immunoglobulins. The binding of the IgG autoantibodies from IVIg to native human liver antigens was blocked not only by a F(ab′)2‐dependent mechanism by circulating IgM and IgG (as has been previously suggested), but also by serum IgA. This control of anti‐self reactivity may be inefficient in some autoimmune diseases.
Clinical correlates of submicroscopic deletions involving the ABL–BCR translocation region in chronic myeloid leukemia
Authors: Yoong Yinlee , VanDeWalker Todd J. , Carlson Richard O. , Dewald Gordon W. , Tefferi Ayalew
Published: January 2005

Abstract:  Recent reports indicate a prognostically detrimental effect of submicroscopic abl–bcr deletions associated with the break and fusion points of the derivative chromosome 9 [der(9)] in chronic myeloid leukemia (CML). In a retrospective cohort of 92 patients with CML, the incidence of an atypical D‐FISH pattern, that is consistent with a der(9) deletion was 20%. Complete clinical information was available in 82 patients and revealed no significant differences between 18 deleted and 64 non‐deleted cases in platelet count, circulating blast percentage, spleen size, or karyotype profile at presentation. However, der(9)‐deleted patients presented with significantly lower hemoglobin levels and higher leukocyte counts. At a median follow‐up of 31 months, the incidence of disease transformation, drug therapy response, and survival were similar between the two groups. These results are contrary to previous reports that suggested inferior survival as well as poor response to alpha interferon therapy in CML patients carrying der(9) deletions.
Single‐agent thalidomide induces response in T‐cell lymphoma
Authors: Damaj G. , Bouabdallah R. , Vey N. , Bilger K. , Mohty M. , Gastaut J. A.
Published: January 2005

Abstract:  T‐cell lymphoma is an aggressive lymphoma that cannot be cured despite aggressive therapy, including autologous stem cell transplantation. Thalidomide is an immunomodulatory drug with numerous properties that has proven effective in relapsed multiple myeloma and, to a lesser extent, in other hematologic diseases. We report three cases of relapsed refractory T‐cell lymphoma treated with thalidomide with a good tumor response.
Autografting followed by a reduced‐intensity conditioning unrelated donor cord blood transplantation for a patient with refractory multiple myeloma: successful engraftment with minimal toxicity
Authors: Ando Toshihiko , Yujiri Toshiaki , Tominaga Takayuki , Shinya Sonoe , Takahashi Toru , Nomiyama Jun , Seguchi Masato , Matsubara Atsushi , Fujii Yasuhiko , Tanizawa Yukio
Published: January 2005

Abstract:  We report on a 59‐yr‐old man with recurrent multiple myeloma. To reduce treatment‐related mortality, while retaining the cytoreductive effects of high‐dose chemotherapy, as well as graft vs. myeloma effect, we used a reduced‐intensity conditioning umbilical cord blood (CB) transplantation following high‐dose chemotherapy with autologous stem cell transplantation support. This patient was engrafted rapidly and extramedullary toxicities were acceptable. Although he had local recurrence in the right calf on day +130 after the CB transplantation, the tumor was successfully treated with radiation therapy, and he is alive and well at present (day +480).
Relatively favorable outcomes of post‐transplant pulmonary function in patients with chronic myeloid leukemia receiving non‐myeloablative allogeneic hematopoietic stem cell transplantation
Authors: Lee M. Y. , Chiou T. J. , Yang M. H. , Bai L. Y. , Hsiao L. T. , Chao T. C. , Tung S. L. , Wang W. S. , Yen C. C. , Liu J. H. , Chen P. M.
Published: January 2005

Abstract:  Pulmonary function tests were performed in 20 patients with chronic myeloid leukemia before and after human leukocyte antigen‐matched allogeneic sibling hematopoietic stem cell transplantation (HSCT) to identify any conditioning treatment effects on post‐transplant function from January 1995 to December 2002. Of 20 patients, eight received non‐myeloablative conditioning treatment and 12 received conventional myeloablative conditioning treatment. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and diffusion capacity for carbon monoxide (DLCO) were performed pretransplant, 6 and 12 months post‐transplant. Possible pre‐HSCT and post‐HSCT risk factors were evaluated for association with pulmonary function. The results showed that myeloablative conditioning treatment had greater negative impact on FEV1, FVC, and DLCO than non‐myeloablative conditioning therapy. We conclude that non‐myeloablative allogeneic HSCT may apply a better transplant choice in patients who need special concern with post‐transplant pulmonary function changes.
Long‐term analysis of the palliative benefit of 2‐chlorodeoxyadenosine for myelofibrosis with myeloid metaplasia
Authors: Faoro Leonardo N. , Tefferi Ayalew , Mesa Ruben A.
Published: January 2005

Abstract:  Objective: Therapeutic splenectomy in myelofibrosis with myeloid metaplasia (MMM) may result in extreme thrombocytosis and leukocytosis and accelerated hepatomegaly. We previously described initial palliative benefit from 2‐chlorodeoxyadenosine (2‐CdA) in such instances. The purpose of this study is to provide long‐term follow‐up on the durability of response in the initial cohort and in additional subsequent cases. Methods: We retrospectively identified patients with histologically confirmed MMM who had palliative therapy with 2‐CdA. Clinical characteristics and information on subsequent clinical course were abstracted at the time of diagnosis of MMM and at initiation of 2‐CdA therapy until death. Results: To date, we have used 2‐CdA as palliative therapy in 14 patients with MMM. After a median of four cycles of therapy, responses for hepatomegaly occurred in 56% of patients, thrombocytosis 50%, leukocytosis 55%, and anemia 40%. Cytopenias were frequent but usually transient and without clinical consequence. Responses occurred usually by the second cycle; median duration of response was 6 months (range, 2–19) after completion of 2‐CdA therapy. Conclusion: This study confirmed relevant and frequently durable palliation of symptoms in about half the patients. 2‐CdA is a reasonable palliative option in postsplenectomy patients with MMM who have problematic myeloproliferation.
Insulin‐like growth factor‐1 is a predictor of blood haemoglobin concentration in 70‐yr‐old subjects
Authors: Nilsson‐Ehle Herman , Bengtsson Bengt‐Åke , Lindstedt Göran , Mellström Dan
Published: January 2005

Abstract:  The role of growth hormone (GH) for maintaining normal erythropoiesis among non‐GH‐deficient elderly subjects is not known. Objectives: To determine relationships between the concentrations of serum insulin‐like growth factor‐1 (IGF‐1) and it's carrier protein insulin‐like growth factor binding protein 3 (IGFBP‐3), as well as plasma erythropoietin (EPO), and blood haemoglobin (Hb) in elderly subjects. Methods: Serum IGF‐1 and IGFBP‐3 and plasma EPO were, in addition to basal haematological tests, measured in a community based representative population sample of 70‐yr‐olds (n = 619; 317 women and 302 men). Statistical analyses were made before and after exclusion of non‐healthy subjects. Results: Mean IGF‐1 concentration was higher among men than women (155 vs. 138 μg/L, P = 0.0000), and that of IGFBP3 lower (2.21 vs. 2.65 mg/L, P = 0.0000). Exclusion of subjects with demonstrable disorders did not significantly influence the distributions of serum‐IGF‐1 and serum‐BP‐3. Hb concentration was positively correlated to concentrations of IGF‐1 (r = 0.15, P < 0.01 for the men; r = 0.34, P < 0.001 for the women), and IGFBP‐3 (r = 0.07, n.s. for the men; r = 0.27, P < 0.001 for the women), and negatively correlated to EPO concentration (r = −0.34, P < 0.001 for the men; r = −0.42, P < 0.001 for the women). In multivariate analysis, serum concentrations of IGF‐1, iron, and plasma concentrations of EPO were independently correlated to Hb among both men and women. Conclusion: GH and/or IGF‐1 are, independently from EPO and regardless of health status and sex, a significant determinant of Hb in elderly subjects.
Prevalence of hepatitis B and C virus infection in haematological malignancies and liver injury following chemotherapy
Authors: Takai Shinji , Tsurumi Hisashi , Ando Kazuki , Kasahara Senji , Sawada Michio , Yamada Toshiki , Hara Takeshi , Fukuno Kenji , Takahashi Takeshi , Oyama Masami , Onishi Hiroo , Tomita Eiichi , Takami Tsuyoshi , Imawari Michio , Moriwaki Hisataka
Published: January 2005

Abstract:  The aim of this study was to determine the carrier rate of hepatitis virus in patients with haematological malignancies and the incidence of liver injury in these patients following chemotherapy. From January 1996 to September 2002, we studied 601 consecutive, unselected series of patients with haematological malignancies admitted in our hospital unit (Japan). They consisted of 246 cases of acute leukaemia, 218 non‐Hodgkin's lymphoma (NHL), 13 adult T‐cell leukaemia, and 124 multiple myeloma. Of these 601 patients, 373 were men and 228 were women; their mean age was 61 yr, with a range from 18 to 89 yr. The prevalences of hepatitis B virus (HBV) and hepatitis C virus (HCV) were 7.3% and 10.1%, respectively, in NHL, both higher than those in acute leukaemia (1.7% and 2.9%, P < 0.005) and in general Japanese population (1.2% and 2.6%). The incidence of post‐chemotherapy liver injury in 25 HBV carriers (36.0%) was significantly higher than that in 539 non‐hepatitis virus carriers (12.6%, P = 0.003) and 37 HCV carriers (10.8%, P = 0.026). Liver injury in HBV carriers was more often present in patients who had been treated with steroids than in those without steroids (72.7% and 0%, P = 0.013). After lamivudine became available in our institution, the incidence of liver injury in HBV carriers was reduced from 53.3% to 10.0% (P = 0.041). The therapeutic strategy for haematological malignancies in hepatitis virus carriers should be further investigated.
Genetic study of the myelin oligodendrocyte glycoprotein (MOG) gene in schizophrenia
Authors: Zai G. , King N. , Wigg K. , Couto J. , Wong G. W. H. , Honer W. G. , Barr C. L. , Kennedy J. L.
Published: January 2005

Schizophrenia (SCZ) is a neuropsychiatric disorder that affects approximately 1% of the general population. The human leukocyte antigen (HLA) system has been implicated in several genetic studies of SCZ. The myelin oligodendrocyte glycoprotein (MOG) gene, which is located close to the HLA region, is considered a candidate for SCZ due to its association with white matter abnormalities and its importance in mediating the complement cascade. Four polymorphisms in the MOG gene (CA)n (TAAA)n, and two intronic polymorphisms, C1334T and C10991T, were investigated for the possibility of association with SCZ using 111 SCZ proband and their families. We examined the transmission of the alleles of each of these polymorphisms with the transmission disequilibrium test. We did not observe significant evidence for biased transmission of alleles at the (CA)n (χ2 = 2.430, 6 df, P = 0.876) (TAAA)n (χ2 = 3.550, 5 df, P = 0.616), C1334T (χ2 = 0.040, 1 df, P = 0.841) and C10991T (χ2 = 0.154, 1 df, P = 0.695) polymorphisms. Overall haplotype analysis using the TRANSMIT program was also not significant (χ2 = 7.954, 9 df, P = 0.539). Furthermore, our results comparing mean age at onset in the genotype groups using the Kruskal–Wallis Test were not significant. Our case‐control analyses (182 cases age‐, sex‐ and ethnicity‐matched with healthy controls) and combined z‐score [(CA)n: z‐score =−1.126, P = 0.130; (TAAA)n: z‐score = −0.233, P = 0.408; C1334T: z‐score = 0.703, P = 0.241; C10991T: z‐score = 0.551, P = 0.291] were also not significant. Although our data are negative, the intriguing hypothesis for MOG in SCZ may warrant further investigation of this gene.
Gene expression in the hippocampus of inbred alcohol‐preferring and ‐nonpreferring rats
Authors: Edenberg H. J. , Strother W. N. , McClintick J. N. , Tian H. , Stephens M. , Jerome R. E. , Lumeng L. , Li T.‐K. , McBride W. J.
Published: January 2005

The hippocampus is sensitive to the effects of ethanol and appears to have a role in the development of alcohol tolerance. The objective of this study was to test the hypothesis that there are innate differences in gene expression in the hippocampus of inbred alcohol‐preferring (iP) and ‐nonpreferring (iNP) rats that may contribute to differences in sensitivity to ethanol and/or in the development of tolerance. Affymetrix microarrays were used to measure gene expression in the hippocampus of alcohol‐naïve male iP and iNP rats in two experiments (n = 4 and 6 per strain in the two experiments). Combining data from the two experiments, there were 137 probesets representing 129 genes that significantly differed (P ≤ 0.01); 62 probesets differed at P ≤ 0.001. Among the 36% of the genes that were expressed more in the iP than iNP rat at this level of significance, many were involved in cell growth and adhesion, cellular stress reduction and anti‐oxidation, protein trafficking, regulation of gene expression, synaptic function and metabolism. Among the 64% of the genes that had lower expression in the hippocampus of iP than iNP rats were genes involved in metabolic pathways, cellular signaling systems, protein trafficking, cell death and neurotransmission. Overall, the data indicate that there are significant innate differences in gene expression in the hippocampus between iP and iNP rats, some of which might contribute to the differences observed in the development of alcohol tolerance between the selectively bred P and NP lines.
Changes in gene expression within the nucleus accumbens and striatum following sexual experience
Authors: Bradley K. C. , Boulware M. B. , Jiang H. , Doerge R. W. , Meisel R. L. , Mermelstein P. G.
Published: January 2005

Sexual experience, like repeated drug use, produces long‐term changes including sensitization in the nucleus accumbens and dorsal striatum. To better understand the molecular mechanisms underlying the neuroadaptations following sexual experience, we employed a DNA microarray approach to identify genes differentially expressed between sexually experienced and sexually naïve female hamsters within the nucleus accumbens and dorsal striatum. For 6 weeks, a stimulus male was placed in the home cage of one‐half of the hormonally primed, ovariectomized female hamsters. On the seventh week, the two experimental groups were subdivided, with one half paired with a stimulus male. In comparison with sexually naïve animals, sexually experienced hamsters receiving a stimulus male on week 7 exhibited an increase in a large number of genes. Conversely, sexually experienced female hamsters not receiving a stimulus male on week 7 exhibited a reduction in the expression of many genes. For directional changes and the categories of genes regulated by the experimental conditions, data were consistent across the nucleus accumbens and dorsal striatum. However, the specific genes exhibiting changes in expression were disparate. These experiments, among the first to profile genes regulated by female sexual behavior, will provide insight into the mechanisms by which both motivated behaviors and drugs of abuse induce long‐term changes in the mesolimbic and nigrostriatal dopamine pathways.
Association and linkage analysis of RGS4 polymorphisms with schizophrenia and bipolar disorder in Brazil
Authors: Cordeiro Q. , Talkowski M. E. , Chowdari K. V. , Wood J. , Nimgaonkar V. , Vallada H.
Published: January 2005

Linkage and association studies in five independently ascertained samples have suggested that polymorphisms of the regulator of G‐protein signaling 4 (RGS4) may confer risk for schizophrenia (SCZ). Suggestive evidence for association with bipolar disorder (BD) has also been presented. However, the associated alleles and haplotypes have differed among the samples. Data from other independent samples may clarify the putative associations. Hence, we investigated an independent, ethnically diverse Brazilian population comprising patients with SCZ (n = 271) or BD1 (n = 306), who were contrasted with 576 community‐based controls. Parents of 49 SCZ cases and 44 BD cases were available for transmission disequilibrium tests (TDTs). Four RGS4 single‐nucleotide polymorphisms (SNPs) 1, 4, 7 and 18 putatively associated with SCZ were investigated. In the SCZ samples, significant case–control differences were not observed for individual SNPs or haplotypes, though the TDT suggested transmission distortion similar to that observed in the initial report. For the BD sample, case–control comparisons revealed no significant differences for individual SNPs, but an omnibus test suggested differences in the overall distribution of haplotypes bearing all four SNPs (SNP‐EM Omnibus likelihood ratio test; P = 0.003). The TDT revealed over‐transmission of allele A at SNP7 (P = 0.016), as well as haplotypes incorporating this allele. However, global tests incorporating all haplotypes yielded only suggestive trends for association (P = 0.19). In conclusion, association with SCZ was not detected in the present analyses. The failure to detect an association may be related to inadequate power or to confounds related to ethnic admixture. Suggestive associations with BD detected here require further investigation in a larger sample.
Predicting radiotherapy‐induced cardiac perfusion defects
Authors: Das Shiva K. , Baydush Alan H. , Zhou Sumin , Miften Moyed , Yu Xiaoli , Craciunescu Oana , Oldham Mark , Light Kim , Wong Terence , Blazing Michael , Borges‐Neto Salvador , Dewhirst Mark W. , Marks Lawrence B.
Published: January 2005

The purpose of this work is to compare the efficacy of mathematical models in predicting the occurrence of radiotherapy‐induced left ventricular perfusion defects assessed using single‐photon emission computed tomography (SPECT). The basis of this study is data from 73 left‐sided breast/chestwall patients treated with tangential photon fields. The mathematical models compared were three commonly used parametric models [Lyman normal tissue complication probability (LNTCP), relative serialty (RS), generalized equivalent uniform dose (gEUD)] and a nonparametric model (Linear discriminant analysis—LDA). Data used by the models were the left ventricular dose—volume histograms, or SPECT‐based dose–function histograms, and the presence/absence of SPECT perfusion defects postradiation therapy (21 patients developed defects). For the parametric models, maximum likelihood estimation and F‐tests were used to fit the model parameters. The nonparametric LDA model step‐wise selected features (volumes/function above dose levels) using a method based on receiver operating characteristics (ROC) analysis to best separate the groups with and without defects. Optimistic (upper bound) and pessimistic (lower bound) estimates of each model's predictive capability were generated using ROC curves. A higher area under the ROC curve indicates a more accurate model (a model that is always accurate has ). The areas under these curves for different models were used to statistically test for differences between them. Pessimistic estimates of areas under the ROC curve using dose–volume histogram/dose–function histogram inputs, in order of increasing prediction accuracy, were LNTCP , RS , gEUD , and LDA . Only the LDA model benefited from SPECT‐based regional functional information. In general, the LDA model was statistically superior to the parametric models. The LDA model selected as features the left ventricular volumes above approximately , essentially volume in field, and , as best separating the groups with and without defects. In conclusion, the nonparametric LDA model appears to be a more accurate predictor of radiotherapy‐induced left ventricular perfusion defects than commonly used parametric models.
Clinical applications of IMRT to adenocarcinoma of the prostate: Portal dose verification and intensity modulated neutron radiotherapy
Authors: Santanam Lakshmi
Published: January 2005

Intensity modulated radiotherapy (IMRT) provides an improvement in the conformality of radiotherapy dose distributions. Its application to photon radiotherapy for prostate adenocarcinoma is well established. A quality assurance tool for verifying photon IMRT treatment and the potential application of intensity modulation to neutron radiotherapy (IMNRT) to prostate cancer are investigated here. This study evaluates the use of an amorphous silicon flat panel imager for dose verification of photon IMRT fields. Various correction factors were developed to allow accurate estimation of the absorbed dose using this portal imager. The ratio of the dose measured with the portal imager to that measured using an ionization chamber was found to be for 23 measured IMRT fields. The study also yielded an accurate estimate of the relative beamlet intensity (fluence) at the plane of the detector. The raw difference between the relative beamlet intensity predicted by the EPID and that of the planning system for 23 IMRT fields was found to be . These results demonstrate the capabilities of this imager as a robust IMRT quality assurance tool. An in‐house optimization algorithm was used to optimize forward planned segments for the treatment of prostate cancer using IMNRT. The applicability of two different algorithms was investigated for IMNRT dose calculation, namely, the differential scatter air ratio (DSAR) and the finite size pencil beam (FSPB) algorithms. Measured profiles and absolute point doses were compared to results calculated by the treatment planning system. Dual ion‐chamber measurements were performed to determine the individual neutron and gamma doses and to estimate the whole body dose equivalent. IMNRT plans retrospectively calculated for five prostate cancer patients provided dose distributions superior to conventional fast neutron therapy. When normalized to provide equivalent target coverage, the volume of the rectum and bladder receiving 80% of the prescription dose in the IMNRT plans was reduced by an average of 16% and 13%, respectively. Measured and calculated profiles for IMNRT fields matched to within with the exception of the penumbral region. Absolute point dose measurements also agreed with calculated doses to within at various points within the modulated dose distribution. Whole body dose estimates for IMNRT plans generated in this study were only an average of 16% higher than conventional fast neutron therapy and no significant variations in RBE are expected based on current measurements. Based on the results presented here, clinical implementation of IMNRT is currently achievable.
Correction of XRII geometric distortion using a liquid‐filled grid and image subtraction
Authors: Holdsworth David W. , Pollmann Steven I. , Nikolov Hristo N. , Fahrig Rebecca
Published: January 2005

X‐ray image intensifier (XRII) geometric distortion reduces the accuracy of image‐guided procedures and quantitative image reconstructions. Due to the dependence of this error on the earth's magnetic field, the required correction is angle dependent, and calibration data should ideally be acquired simultaneously with clinical image data, at a specific orientation. We describe a technique to correct XRII geometric image distortion at any angular position during a stereotactic procedure. This approach uses a machined plastic grid, which contains channels that can be filled with iodinated contrast agent and subsequently flushed with water, providing contrast and mask images, respectively, of a geometric calibration grid. The standard image subtraction capabilities of conventional digital subtraction angiography devices can then be used to create a subtraction image of the iodine‐filled channels, without any confounding anatomical structure. Grid‐line intersection points are used to determine the control points that are required for a global polynomial correction algorithm, creating a correction map that is specific to the current angular position and XRII field of view (FOV). Tests with a clinical ‐arm based XRII show that control points can be obtained with a precision of ±0.053 mm, resulting in geometric correction accuracy of ±0.152 mm, at a nominal FOV of 40 cm. While the precision and accuracy are both poorer than that achieved with a high‐contrast steel‐bead grid, the fact that the liquid grid can remain rigidly attached to the XRII during an entire procedure results in the establishment of an absolute detector coordinate system (referenced to the liquid‐filled correction grid). The design of the liquid‐filled channels allows the required control points to be introduced into the image or removed in about 30 s, avoiding the appearance of obscuring or confounding markers during clinical image acquisition, with a concurrent increase in patient dose of about 8% in the current design. Applications for this technique include stereotactic surgery, radiosurgery, x‐ray stereogrammetry, and other image‐guided procedures.
Dosimetric evaluation of a new design MOSFET in vivo dosimeter
Authors: Halvorsen Per H.
Published: January 2005

A single‐use dosimeter, designed for in vivo patient dosimetry, has been evaluated. Key dosimetric characteristics of the dosimetry system have been measured for high‐energy photon and electron beams commonly used in external beam therapy. Under the measurement conditions utilized, dose accuracy was within 5% for all data points, and inter‐batch uniformity was acceptable, with a standard deviation of 1.7%. Dose linearity was confirmed for doses ranging from . The dosimeter readings were independent of dose rate for rates ranging from . When used as instructed, the dosimeter readings were accurate across the tested range of energy and modality. These measurements show that the dosimetry system's performance may be acceptable for in vivo dosimetry of entrance doses.
Temporal performance of amorphous selenium mammography detectors
Authors: Zhao Bo , Zhao Wei
Published: January 2005

We investigated temporal performance of amorphous selenium (a‐Se) detectors specifically designed for mammographic imaging. Our goal is to quantify the inherent lag and ghosting of a‐Se photoconductor as a function of imaging conditions. Two small area electroded a‐Se samples, one positively and the other negatively biased on the entrance side of x rays, were used in the experiments. The study of lag and ghosting was performed by delivering a number of raw exposures as experienced in screening mammography to the samples at different electric field strength while measuring the current through the a‐Se sample. Ghosting at different operational conditions was quantified as the percentage x‐ray sensitivity (x‐ray generated photocurrent measured from the sample) reduction compared to before irradiation. Lag was determined by measuring the residual current of a‐Se at a given time after the end of each x‐ray exposure. Both lag and ghosting were measured as a function of and cumulative exposure. The values of used in our experiments ranged from 1 to 20 V/μm. It was found that ghosting increases with exposure and decreases with for both samples because of the dominant effect of recombination between trapped electrons and x‐ray generated holes. Lag on the other hand has different dependence on and cumulative exposure. At , the first frame lag for both samples changed slowly with cumulative exposure, with a range of 0.2%–1.7% for the positively biased sample and 0.5%–8% for the negatively biased sample. Overall the positively biased sample has better temporal performance than the negatively biased sample due to the lower density of trapped electrons. The impact of time interval between exposures on the temporal performance was also investigated. Recovery of ghosting with longer time interval was observed, which was attributed to the neutralization of trapped electrons by injected holes through dark current.
Real‐time 3D surface‐image‐guided beam setup in radiotherapy of breast cancer
Authors: Djajaputra David , Li Shidong
Published: January 2005

We describe an approach for external beam radiotherapy of breast cancer that utilizes the three‐dimensional (3D) surface information of the breast. The surface data of the breast are obtained from a 3D optical camera that is rigidly mounted on the ceiling of the treatment vault. This 3D camera utilizes light in the visible range therefore it introduces no ionization radiation to the patient. In addition to the surface topographical information of the treated area, the camera also captures gray‐scale information that is overlaid on the 3D surface image. This allows us to visualize the skin markers and automatically determine the isocenter position and the beam angles in the breast tangential fields. The field sizes and shapes of the tangential, supraclavicular, and internal mammary gland fields can all be determined according to the 3D surface image of the target. A least‐squares method is first introduced for the tangential‐field setup that is useful for compensation of the target shape changes. The entire process of capturing the 3D surface data and subsequent calculation of beam parameters typically requires less than 1 min. Our tests on phantom experiments and patient images have achieved the accuracy of 1 mm in shift and 0.5° in rotation. Importantly, the target shape and position changes in each treatment session can both be corrected through this real‐time image‐guided system.
Compensation of magnetic field distortions from paramagnetic instruments by added diamagnetic material: Measurements and numerical simulations
Authors: Müller‐Bierl Bernd , Graf Hansjörg , Steidle Günter , Schick Fritz
Published: January 2005

In minimally invasive procedures guided by magnetic resonance (MR) imaging instruments usually are made of titanium or titanium alloys (e.g., nitinol), because other more MR‐compatible materials often cannot provide sufficient mechanical properties. Artifacts depending on susceptibility arise in MR images due to incorrect spatial encoding and intravoxel dephasing and thereby hamper the surgeon's view onto the region of interest. To overcome the artifact problem, compensation of the paramagnetic properties by diamagnetic coating or filling of the instruments has been proposed in the literature. We used a numerical modeling procedure to estimate the effect of compensation. Modeling of the perturbation of the static magnetic field close to the instruments reflects the underlying problem and is much faster and cost efficient than manufacturing prototypes and measuring artifact behavior of these prototypes in the MR scanner. A numerical model based on the decomposition of the susceptibility distribution in elementary dipoles was developed by us. The program code was written object oriented to allow for both maximum computational speed and minimum random access memory. We used System International units throughout the modeling for the magnetic field, allowing absolute quantification of the magnetic field disturbance. The field outside a simulated needlelike instrument, modeled by a paramagnetic cylinder (out of titan, ) of length 8.0 mm and of diameter 1.0 mm, coated with a diamagnetic layer (out of bismuth, ) of thickness 0, 0.1, 0.2, 0.3, and 0.4 mm, was found to be best compensated if the cross‐sectional area of the cylinder, multiplied by the absolute susceptibility value of the cylinder material, is equal to the cross‐sectional area of the coating, multiplied by the absolute susceptibility value of the coating material. At the extremity of the coated cylinder an uncompensated field distortion was found to remain. We studied various tip shapes and geometries using our computational model: Suitable diamagnetic coating or filling of paramagnetic instruments clearly reduced tip artifacts and diminished the dependency of artifact size on orientation of the instrument with respect to in the numerical studies. We verified the results of the simulations by measuring coated and uncoated titanium wires in a 1.5 T MR scanner.
The use of film dosimetry of the penumbra region to improve the accuracy of intensity modulated radiotherapy
Authors: Arnfield Mark R. , Otto Karl , Aroumougame Vijayan R. , Alkins Ryan D.
Published: January 2005

Accurate measurements of the penumbra region are important for the proper modeling of the radiation beam for linear accelerator‐based intensity modulated radiation therapy. The usual data collection technique with a standard ionization chamber artificially broadens the measured beam penumbrae due to volume effects. The larger the chamber, the greater is the spurious increase in penumbra width. This leads to inaccuracies in dose calculations of small fields, including small fields or beam segments used in IMRT. This source of error can be rectified by the use of film dosimetry for penumbra measurements because of its high spatial resolution. The accuracy of IMRT calculations with a pencil beam convolution model in a commercial treatment planning system was examined using commissioning data with and without the benefit of film dosimetry of the beam penumbrae. A set of dose‐spread kernels of the pencil beam model was calculated based on commissioning data that included beam profiles gathered with a 0.6‐cm‐i.d. ionization chamber. A second set of dose‐spread kernels was calculated using the same commissioning data with the exception of the penumbrae, which were measured with radiographic film. The average decrease in the measured width of the 80%–20% penumbrae of various square fields of size 3–40 cm, at 5 cm depth in water‐equivalent plastic was 0.27 cm. Calculations using the pencil beam model after it was re‐commissioned using film dosimetry of the penumbrae gave better agreement with measurements of IMRT fields, including superior reproduction of high dose gradient regions and dose extrema. These results show that accurately measuring the beam penumbrae improves the accuracy of the dose distributions predicted by the treatment planning system and thus is important when commissioning beam models used for IMRT.
Validation of Monte Carlo calculated surface doses for megavoltage photon beams
Authors: Abdel‐Rahman Wamied , Seuntjens Jan P. , Verhaegen Frank , Deblois François , Podgorsak Ervin B.
Published: January 2005

Recent work has shown that there is significant uncertainty in measuring build‐up doses in megavoltage photon beams especially at high energies. In this present investigation we used a phantom‐embedded extrapolation chamber (PEEC) made of Solid Water™ to validate Monte Carlo (MC)‐calculated doses in the dose build‐up region for 6 andx‐ray beams. The study showed that the percentage depth ionizations (PDIs) obtained from measurements are higher than the percentage depth doses (PDDs) obtained with Monte Carlo techniques. To validate the MC‐calculated PDDs, the design of the PEEC was incorporated into the simulations. While the MC‐calculated and measured PDIs in the dose build‐up region agree with one another for thebeam, a non‐negligible difference is observed for thex‐ray beam. A number of experiments and theoretical studies of various possible effects that could be the source of this discrepancy were performed. The contribution of contaminating neutrons and protons to the build‐up dose region in thex‐ray beam is negligible. Moreover, the MC calculations using the XCOM photon cross‐section database and the NIST bremsstrahlung differential cross section do not explain the discrepancy between the MC calculations and measurement in the dose build‐up region for the. A simple incorporation of triplet production events into the MC dose calculation increases the calculated doses in the build‐up region but does not fully account for the discrepancy between measurement and calculations for thex‐ray beam.
Imaging of high‐intensity focused ultrasound‐induced lesions in soft biological tissue using thermoacoustic tomography
Authors: Jin Xing , Xu Yuan , Wang Lihong V. , Fang Yuncai R. , Zanelli Claudio I. , Howard Samuel M.
Published: January 2005

An imaging technology, thermoacoustic tomograpy (TAT), was applied to the visualization of high‐intensity focused ultrasound (HIFU)‐induced lesions. A single, spherically focused ultrasonic transducer, operating at a central frequency of approximately 4 MHz, was used to generate a HIFU field in fresh porcine muscle. Microwave pulses from a 3‐GHz microwave generator were then employed to generate thermoacoustic sources in this tissue sample. The thermoacoustic signals were detected by an unfocused ultrasonic transducer that was scanned around the sample. To emphasize the boundaries between the lesion and its surrounding tissue, a local‐tomography‐type reconstruction method was applied to reconstruct the TAT images of the lesions. Good contrast was obtained between the lesion and the tissue surrounding it. Gross pathologic photographs of the tissue samples confirmed the TAT images. This work demonstrates that TAT may potentially be used to image HIFU‐induced lesions in biological tissues.
Visibility of simulated microcalcifications—A hardcopy‐based comparison of three mammographic systemsa)
Authors: Lai Chao‐Jen , Shaw Chris C. , Whitman Gary J. , Johnston Dennis A. , Yang Wei T. , Selinko Veronica , Arribas Elsa , Dogan Basak , Kappadath S. Cheenu
Published: January 2005

Full‐field digital mammography systems are currently available for clinical use. These digital systems offer improved image quality, flexible image processing, display, storage, retrieval, and transmission. These systems employ a variety of different x‐ray detectors based on storage phosphors (in computed radiography), charge‐coupled devices (CCDs), or amorphous silicon flat panels (FPs). The objective of this study is to compare three different types of mammographic detectors: screen–film (SF) combination, a ‐based FP detector, a CCD and x‐ray phosphor‐based detector for their performance in detection of simulated microcalcifications. Microcalcifications (MCs) were simulated with calcium carbonate grains of various sizes . They were overlapped with a slab of simulated 50% adipose/50% glandular breast tissue for a uniform background or an anthropomorphic breast phantom for a tissue structure background. Images of the phantoms, acquired with and without magnification, were reviewed by mammographers, physicists, and students. A five‐point confidence level rating was given for each MC reviewed. Average ratings from the mammographers were used to compare the performances of the three imaging systems, various MC size groups, and two magnification modes. The results indicate that with uniform background and no magnification, the FP system performed the best while the SF system did slightly better than the CCD system. With magnification added, all detection tasks were improved except for the smallest and largest one or two size groups. In particular, detection in the SF and CCD images was significantly improved over that in the FP images. With tissue structure background and no magnification, the FP system was outperformed by the SF and the CCD systems. With magnification added, the performance of the FP and the CCD systems was improved significantly. With this improvement, the SF and FP systems were outperformed by the CCD system.
Patient specific optimization of the relation between CT‐Hounsfield units and proton stopping power with proton radiography
Authors: Schneider Uwe , Pemler Peter , Besserer Jürgen , Pedroni Eros , Lomax Antony , Kaser‐Hotz Barbara
Published: January 2005

The purpose of this work is to show the feasibility of using in vivo proton radiography of a radiotherapy patient for the patient individual optimization of the calibration from CT‐Hounsfield units to relative proton stopping power. Water equivalent tissue (WET) calibrated proton radiographs of a dog patient treated for a nasal tumor were used as baseline in comparison with integrated proton stopping power through the calibrated CT of the dog. In an optimization procedure starting with a stoichiometric calibration curve, the calibration was modified randomly. The result of this iteration is an optimized calibration curve which was used to recalculate the dose distribution of the patient. One result of this experiment was that the mean value of the deviations between WET calculations based on the stoichiometric calibration curve and the measurements was shifted systematically away from zero. The calibration produced by the optimization procedure reduced this shift to around . Another result was that the precision of the calibration, reflected as the standard deviation of the normally distributed deviations between WET calculation and measurement, could be reduced from 7.9 to with the optimized calibration. The dose distributions based on the two calibration curves showed major deviations at the distal end of the target volume.
Dose perturbation of a novel cobalt chromium coronary stent on intravascular brachytherapy: A Monte Carlo study
Authors: Mourtada Firas , Horton John L.
Published: January 2005

Intravascular brachytherapy has been adopted for the indication of in‐stent restenosis on the basis of results of clinical trials using mainly stainless steel stents. Recently, a new stent made of cobalt‐chromium L‐605 alloy (, ) (MULTI‐LINK VISION™) was introduced as an alternative to the 316L stainless steel stent design (SS, ) (MULTI‐LINK PENTA™). In this work, we used the Monte Carlo code MCNPX to compare the dose distribution for the GALILEO™ source in and SS stent models. The dose perturbation factor (DPF), defined as the ratio of the dose in water with the presence of a stent to the dose without a stent, was used to compare results. Both stent designs were virtually expanded to diameters of 2.0, 3.0, and using finite element models. The complicated strut shapes of both the and SS stents were simplified using circular rings with an effective width to yield a metal‐to‐tissue ratio identical to that of the actual stents. The mean DPF at a tissue depth, over the entire stented length of , was 0.935 for the stent and 0.911 for the SS stent. The mean DPF at the intima ( radial distance from the strut outer surface), over the entire stented length of , was 0.950 for , and 0.926 for SS. The maximum DPFs directly behind the and SS struts were 0.689 and 0.644, respectively. All DPF estimates have a standard deviation of , approximating the 95% confidence interval. Although the stent has a higher effective atomic number and greater density than the SS stent, the DPFs for the two stents are similar, probably because the metal‐to‐tissue ratio and strut thickness of the stent are lower than those of the SS stent.
Theoretical signal‐to‐noise ratio and spatial resolution dependence on the magnetic field strength for hyperpolarized noble gas magnetic resonance imaging of human lungs
Authors: Parra‐Robles Juan , Cross Albert R. , Santyr Giles E.
Published: January 2005

In hyperpolarized noble gas (HNG) magnetic resonance (MR) imaging, the available polarization is independent of magnetic field strength and for large radiofrequency (rf) coils, such as those used for chest imaging, the body noise becomes the primary noise source making signal‐to‐noise ratio (SNR) largely frequency independent at intermediate field strengths . Furthermore, the reduction in the transverse relaxation time, , of HNG in lungs with increasing field strength, results in a decrease in the achievable SNR at higher fields. In this work, the optimum field strength for HNG MR imaging was theoretically calculated in terms of both SNR and spatial resolution. SNR calculations used the principle of reciprocity and included contributions to the noise arising from both coil and sample losses in a chest‐sized coil for lung imaging. The effects of susceptibility differences, transverse relaxation time, and diffusion were considered in the resolution calculations. The calculations show that the optimum field strength for HNG MR imaging of human lungs is between 0.1 and depending on gas type (helium or xenon) and sample size. At the field strengths currently used by conventional clinical proton MR imaging systems , the predicted SNR are 10%–50% lower than at the optimum field with only slightly worse spatial resolution (10%–20%). At higher fields , however, the SNR degrades considerably reducing the achievable spatial resolution. Although HNG of the lung is still feasible at very low field strengths , the available SNR is much lower than at optimum fields and this reduces the achievable spatial resolution. These findings suggest that HNG imaging may be optimally performed at much lower field strengths than conventional clinical proton MR imaging systems. This could considerably decrease cost, improve patient access, and reduce chemical shift and susceptibility artifacts and rf heating.