Alan H. Stolpen

Response Assessment of Aggressive Non-Hodgkin’s Lymphoma by Integrated International Workshop Criteria and Fluorine-18–Fluorodeoxyglucose Positron Emission Tomography

PURPOSE To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a more accurate response assessment than IWC alone in patients with non-Hodgkins lymphoma (NHL). PATIENTS AND METHODS Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations. RESULTS By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio [HR], 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis. CONCLUSION Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.

Liver tumor characterization: Comparison between liver-specific gadoxetic acid disodium-enhanced MRI and biphasic CT - A multicenter trial

Objective: In our multi center trial we compared the potentials of biphasic contrast-enhanced computed tomography (CT) and a novel tissue-specific magnetic resonance imaging (MRI) contrast agent gadoxetic acid disodium in liver lesion characterization. Methods: A total of 176 patients with 252 liver lesions were analyzed. There were 104 malignant and 148 benign lesions. High-field strength (1.0 T or 1.5 T) MR systems with T1-and T2-weighted sequences were used with and without fat suppression. After gadoxetic acid disodium injection, dynamic imaging and hepatocyte phase MR imaging were performed. Biphasic with 150 mg I/kg of body weight (100-200 mL) spiral CT was also performed. Image reading consisted of on-site (by study investigators) and fully blinded off-site (by E.S.P; C.R; and A.S) evaluations. The classification (benign or malignant) and characterization (lesion type) outcomes of both techniques were assessed. All imaging results were verified against a standard of reference. Results: Both on-site and off-site evaluations demonstrated increases in the lesion classification accuracy with gadoxetic acid disodium-enhanced MRI when compared with spiral CT. This improvement was also shown for characterization. Gadoxetic acid disodium was well tolerated. Conclusions: Gadoxetic acid disodium offers a safe and diagnostically powerful tool for the evaluation of patients with focal liver lesions with a reliable assessment of lesion classification and characterization.

Breast MRI lesion classification: improved performance of human readers with a backpropagation neural network computer-aided diagnosis (CAD) system.

To develop and test a computer‐aided diagnosis (CAD) system to improve the performance of radiologists in classifying lesions on breast MRI (BMRI).

Older donor livers show early severe histological activity, fibrosis, and graft failure after liver transplantation for hepatitis C.

Background. In hepatitis C virus (HCV)-positive liver transplant recipients, infection of the allograft and recurrent liver disease are important problems. Increased donor age has emerged as an important variable affecting patient and graft survival; however, specific age cutoffs and risk ratios for poor histologic outcomes and graft survival are not clear. Methods. A longitudinal database of all HCV-positive patients transplanted at our center during an 11-year period was used to identify 111 patients who received 124 liver transplants. Graft survival and histological endpoints (severe activity and fibrosis) of HCV infection in the allografts were compared as a function of donor age at transplantation. Results. By Kaplan-Meier analyses, older allografts showed earlier failure and decreased time to severe histological activity and fibrosis as compared with allografts from younger donors. By Cox proportional hazards analysis, older allografts were at greater risk for all severe histologic features and decreased graft survival as compared with younger allografts (P≤0.02 for all outcomes). Analysis of donor age as a dichotomous variable showed that donors greater than 60 yr were at high risk for deleterious histologic outcomes and graft failure. An age cutoff of 60 yr showed a sensitivity of 94% and specificity of 67% for worse graft survival by receiver operating characteristics curve. Conclusions. Advanced donor age is associated with more aggressive recurrent HCV and early allograft failure in HCV-positive liver transplant recipients. Consideration of donor age is important for decisions regarding patient selection, antiviral therapy, and organ allocation.

DYNAMIC MAGNETIC RESONANCE IMAGING OF THE FEMALE PELVIS: THE RELATIONSHIP WITH THE PELVIC ORGAN PROLAPSE QUANTIFICATION STAGING SYSTEM

PURPOSE Magnetic resonance imaging (MRI) was performed to determine anatomical correlations with respect to physical examination using the Pelvic Organ Prolapse (POP) staging system. In addition, the standard POP staging system was analyzed to obtain normative data and determine any risk factors for prolapse. MATERIALS AND METHODS A total of 52 continent women 19 to 67 years old participated in our study. Pelvic MRI was performed at 1.5 Tesla. The vagina, bladder and rectum were opacified. Subjects performed pelvic floor contraction, relaxation and straining maneuvers for T1-weighted imaging. One-way analysis of variance, Fishers exact test and multinomial logistic regression were used to analyze the data. RESULTS POP stage is quantified from 0 to IV. Stage was 0 to II in 56%, 27% and 17% of cases. POP stage was not significantly influenced by the number of cesarean sections (p = 0.64) or smoking (p = 0.91) but the number of vaginal deliveries significantly correlated with stage. Women with 1 vaginal delivery were at increased risk for a stage I condition (p = 0.018), whereas those with more than 1 were at increased risk for stage II (p = 0.013). On MRI stages 0 versus I or II differed significantly in regard to bladder descent (p = 0.01 and <0.0001, respectively), while stages 0 versus I differed in regard to levator angle (p = 0.007). No significant staging differences were observed in regard to the posterior urethrovesical angle or stages I versus II with respect to all 3 MRI measurements. CONCLUSIONS MRI appears to detect anatomically measurable changes in POP stage 0 versus other stages in regard to bladder descent and the levator angle and yet it is not sensitive enough to detect differences in stages I and II. It is not unusual for continent women to have a moderate degree of pelvic prolapse and previous vaginal delivery appears to increase this risk.

Evaluation of locally recurrent pelvic malignancy: Performance of T2- and diffusion-weighted MRI with image fusion

To evaluate the performance of T2‐ and diffusion‐weighted magnetic resonance imaging (MRI) with image fusion for detection of locally recurrent pelvic malignancy.

Congenital aortic disease: 4D magnetic resonance segmentation and quantitative analysis

Automated and accurate segmentation of the aorta in 4D (3D+time) cardiovascular magnetic resonance (MR) image data is important for early detection of congenital aortic disease leading to aortic aneurysms and dissections. A computer-aided diagnosis (CAD) method is reported that allows one to objectively identify subjects with connective tissue disorders from 16-phase 4D aortic MR images. Starting with a step of multi-view image registration, our automated segmentation method combines level-set and optimal surface segmentation algorithms in a single optimization process so that the final aortic surfaces in all 16 cardiac phases are determined. The resulting aortic lumen surface is registered with an aortic model followed by calculation of modal indices of aortic shape and motion. The modal indices reflect the differences of any individual aortic shape and motion from an average aortic behavior. A Support Vector Machine (SVM) classifier is used for the discrimination between normal and connective tissue disorder subjects. 4D MR image data sets acquired from 104 normal volunteers and connective tissue disorder patients MR datasets were used for development and performance evaluation of our method. The automated 4D segmentation resulted in accurate aortic surfaces in all 16 cardiac phases, covering the aorta from the aortic annulus to the diaphragm, yielding subvoxel accuracy with signed surface positioning errors of -0.07+/-1.16 voxel (-0.10+/-2.05mm). The computer-aided diagnosis method distinguished between normal and connective tissue disorder subjects with a classification correctness of 90.4%.

Segmentation of wall and plaque in in vitro vascular MR images.

Atherosclerosis leads to heart attack and stroke, which are major killers in the western world. These cardiovascular events frequently result from local rupture of vulnerable atherosclerotic plaque. Non-invasive assessment of plaque vulnerability would dramatically change the way in which atherosclerotic disease is diagnosed, monitored, and treated. In this paper, we report a computerized method for segmentation of arterial wall layers and plaque from high-resolution volumetric MR images. The method uses dynamic programming to detect optimal borders in each MRI frame. The accuracy of the results was tested in 62 T1-weighted MR images from six vessel specimens in comparison to borders manually determined by an expert observer. The mean signed border positioning errors for the lumen, internal elastic lamina, and external elastic lamina borders were −0.1 ± 0.1, 0.0 ± 0.1, and −0.1 ± 0.1 mm, respectively. The presented wall layer segmentation approach is one of the first steps towards non-invasive assessment of plaque vulnerability in atherosclerotic subjects.

Reproducibility of Dynamic MR Imaging Pelvic Measurements : A Multi-institutional Study

PURPOSE To assess the reproducibility of bone and soft-tissue pelvimetry measurements obtained from dynamic magnetic resonance (MR) imaging studies in primiparous women across multiple centers. MATERIALS AND METHODS All subjects prospectively gave consent for participation in this institutional review board-approved, HIPAA-compliant study. At six clinical sites, standardized dynamic pelvic 1.5-T multiplanar T2-weighted MR imaging was performed in three groups of primiparous women at 6-12 months after birth: Group 1, vaginal delivery with anal sphincter tear (n = 93); group 2, vaginal delivery without anal sphincter tear (n = 79); and group 3, cesarean delivery without labor (n = 26). After standardized central training, blinded readers at separate clinical sites and a blinded expert central reader measured nine bone and 10 soft-tissue pelvimetry parameters. Subsequently, three readers underwent additional standardized training, and reread 20 MR imaging studies. Measurement variability was assessed by using intraclass correlation for agreement between the clinical site and central readers. Acceptable agreement was defined as an intraclass correlation coefficient (ICC) of at least 0.7. RESULTS There was acceptable agreement (ICC range, 0.71-0.93) for eight of 19 MR imaging parameters at initial readings of 198 subjects. The remaining parameters had an ICC range of 0.13-0.66. Additional training reduced measurement variability: Twelve of 19 parameters had acceptable agreement (ICC range, 0.70-0.92). Correlations were greater for bone (ICC, >or=0.70 in five [initial readings] and eight of nine [rereadings] variables) than for soft-tissue measurements (ICC, >or=0.70 in three [initial readings] of 10 and four [rereadings] of 10 readings, respectively). CONCLUSION Despite standardized central training, there is high variability of pelvic MR imaging measurements among readers, particularly for soft-tissue structures. Although slightly improved with additional training, measurement variability adversely affects the utility of many MR imaging measurements for multicenter pelvic floor disorder research.

Prospective Cohort Study of Nephrogenic Systemic Fibrosis in Patients With Stage 3–5 Chronic Kidney Disease Undergoing MRI With Injected Gadobenate Dimeglumine or Gadoteridol

OBJECTIVE The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD) and moderate-to-severe impairment of kidney function who had not previously been exposed to gadolinium-based contrast agents (GBCAs) or referred to undergo contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol. SUBJECTS AND METHODS Two multicenter prospective cohort studies evaluated the incidence of unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration rate [eGFR] in cohort 1, 30-59 mL/min/1.73 m(2)) or stage 4 or 5 CKD (eGFR in cohort 2, < 30 mL/min/1.73 m(2)) after injection of gadobenate dimeglumine (study A) or gadoteridol (study B). A third study (study C) determined the incidence of NSF in patients with stage 4 or 5 CKD who had not received a GBCA in the 10 years before enrollment. Monitoring for signs and symptoms suggestive of NSF was performed via telephone at 1, 3, 6, and 18 months, with clinic visits occurring at 1 and 2 years. RESULTS For studies A and B, the populations evaluated for NSF comprised 363 and 171 patients, respectively, with 318 and 159 patients in cohort 1 of each study, respectively, and with 45 and 12 patients in cohort 2, respectively. No signs or symptoms of NSF were reported or detected during the 2 years of patient monitoring. Likewise, no cases of NSF were reported for any of the 405 subjects enrolled in study C. CONCLUSION To our knowledge, and consistent with reports in the literature, no association of gadobenate dimeglumine or gadoteridol with unconfounded cases of NSF has yet been established. Study data confirm that both gadoteridol and gadobenate dimeglumine properly belong to the class of GBCAs considered to be associated with the lowest risk of NSF.