Faculty Bibliography

OBJECTIVE: To test the hypothesis that diffuse abnormalities precede axonal damage and atrophy in the MRI normal-appearing tissue of relapsing-remitting (RR) multiple sclerosis (MS) patients, and that these processes continue during clinical remission. METHODS: Twenty-one recently diagnosed mildly disabled (mean disease duration 2.3 years, mean Expanded Disability Status Scale score of 1.4) RR MS patients and 15 healthy matched controls were scanned with MRI and proton MR spectroscopic imaging ((1)H-MRSI) at 3 T. Metabolite concentrations: N-acetylaspartate (NAA) for neuronal integrity; choline (Cho) for membrane turnover rate; creatine (Cr) and myo-inositol (mI) for glial status were obtained in a 360 cm(3) volume of interest (VOI) with 3D multivoxel (1)H-MRSI. They were converted into absolute amounts using phantom replacement and normalised into absolute concentrations by dividing by the VOI tissue volume fraction obtained from MRI segmentation. RESULTS: The patients' mean VOI tissue volume fraction, 0.92 and NAA concentration, 9.6 mM, were not different from controls' 0.94 and 9.6 mM. In contrast, the patients' mean Cr, Cho and mI levels 7.7, 1.9 and 4.1 mM were 9%, 14% and 20%, higher than the controls' 7.1, 1.6 and 3.4 mM (p = 0.0097, 0.003 and 0.0023). CONCLUSIONS: The absence of early tissue atrophy and apparent axonal dysfunction (NAA loss) in these RR MS patients suggests that both are preceded by diffuse glial proliferation (astrogliosis), as well as possible inflammation, demyelination and remyelination reflected by elevated mI, Cho and Cr, even during clinical remission and despite immunomodulatory treatment

OBJECTIVE: The purpose of our study was to determine the findings at both static and dynamic MRI in women with a clinically suspected urethral abnormality. MATERIALS AND METHODS: MRI of the urethra was performed in 84 women with lower urinary tract symptoms using multiplanar T2-weighted turbo spin-echo and unenhanced and contrast-enhanced gradient-echo sequences. A dynamic true fast imaging with steady-state free precession sequence was performed during straining in the sagittal plane. Images were evaluated by two radiologists for urethral pathology and pelvic organ prolapse. MRI findings were correlated with clinical symptoms using the Fisher's exact and Mann-Whitney tests. RESULTS: Urethral abnormalities were found in 10 of 84 patients (11.9%), including two urethral diverticula, five Skene's gland cysts or abscesses, and three periurethral cysts. Thirty-three patients (39.3%) were diagnosed with pelvic organ prolapse, of whom 29 (87.9%) were diagnosed exclusively on dynamic imaging. In 29 of 33 patients with prolapse (87.9%), the urethra was structurally normal. MRI showed 13 cystoceles and 17 cases of urethral hypermobility not detected on physical examination. Patients with a greater number of vaginal deliveries, stress urinary incontinence, frequency of voiding, and voiding difficulty were statistically more likely to have anterior compartment prolapse (p < 0.05). CONCLUSION: Including a dynamic sequence permits both structural and functional evaluation of the urethra, which may be of added value in women with lower urinary tract symptoms. Dynamic MRI allows detection of pelvic organ prolapse that may not be evident on conventional static sequences

OBJECTIVE: The objective of this study was to quantitatively assess cartilage degeneration via T2 mapping to compare patients with and those without meniscal tears. SUBJECTS AND METHODS: Thirty-seven patients (18 men, mean age +/- SD, 65.7 +/- 7.8 years; 19 women, mean age, 63.8 +/- 12.0 years) with clinical symptoms of osteoarthritis were studied on 3-T MRI using a 2D multiecho spin-echo sequence for T2 mapping. Meniscal signal and morphology were qualitatively graded and correlated to the T2 values of cartilage. Analysis of covariance, Bonferroni multiple comparison correction, and Spearman's correlation coefficients were used for statistical analysis. RESULTS: Patients with meniscal tears (median +/- interquartile range, 50.1 +/- 6.1 milliseconds) had significantly (p = 0.021) higher T2 values of cartilage than those without meniscal tears (45.7 +/- 4.8 milliseconds). T2 values of cartilage were significantly higher in the medial compartment than in the lateral compartment in patients with medial meniscal tears (p = 0.018). CONCLUSION: T2 measurements are increased in patients with meniscal tears; this finding adds support to the theory of an association of osteoarthritis with damage to both the menisci and hyaline cartilage

OBJECTIVE: The purpose of this study was to conduct, using histopathologic examination as the reference standard, a preliminary evaluation of the use of a breath-hold multiecho T2(*)-weighted MRI sequence in the detection and quantification of hepatic iron deposition in patients with liver disease. MATERIALS AND METHODS: The images of 43 patients with liver disease who underwent 1.5-T MRI of the liver that included a multiecho T2(*)-weighted sequence who also underwent concomitant liver biopsy or liver transplantation were assessed. Two independent observers measured hepatic T2(*) by placing regions of interest in the hepatic parenchyma. Hepatic T2(*) values were compared between patients stratified by hepatic iron grade and were correlated with histopathologic iron grade. Receiver operating characteristics analysis was performed to assess the accuracy of images obtained with the hepatic T2(*)-weighted sequence in the diagnosis of iron deposition. RESULTS: Patients with iron deposition had shorter hepatic T2(*) values than did patients without iron deposition (mean T2(*), 17.7 vs 32.3 milliseconds with pooled data from both observers; p < 0.0001). Patients with iron grade 3 or greater had shorter T2(*) values than those with iron grade 2 or less (10.1 vs 20.8 milliseconds; p < 0.0001). There was a strong negative correlation between hepatic T2(*) and histopathologic iron grade (r = -0.849; p < 0.0001). For the prediction of iron grades 1 or greater and 3 or greater, area under the curve, sensitivity, and specificity were 0.968-0.982, 90.5-100%, and 100-97.3% at T2(*) cutoffs of less than 24 and less than 14 milliseconds, respectively. CONCLUSION: Hepatic iron overload in patients with liver disease can be assessed rapidly and accurately with MRI performed with a breath-hold T2(*)-weighted sequence

The structure and metabolism of the rhesus macaque brain, an advanced model for neurologic diseases and their treatment response, is often studied noninvasively with MRI and (1)H-MR spectroscopy. Due to the shorter transverse relaxation time (T(2)) at the higher magnetic fields these studies favor, the echo times used in (1)H-MR spectroscopy subject the metabolites to unknown T(2) weighting, decreasing the accuracy of quantification which is key for inter- and intra-animal comparisons. To establish the 'baseline' (healthy animal) T(2) values, we mapped them for the three main metabolites' T(2)s at 3 T in four healthy rhesus macaques and tested the hypotheses that their mean values are similar (i) among animals; and (ii) to analogs regions in the human brain. This was done with three-dimensional multivoxel (1)H-MR spectroscopy at (0.6 x 0.6 x 0.5 cm)(3) = 180 microL spatial resolution over a 4.2 x 3.0 x 2.0 = 25 cm(3) ( approximately 30%) of the macaque brain in a two-point protocol that optimizes T(2) precision per unit time. The estimated T(2)s in several gray and white matter regions are all within 10% of those reported in the human brain (mean +/- standard error of the mean): N-acetylaspartate = 316 +/- 7, creatine = 177 +/- 3, and choline = 264 +/- 9 ms, with no statistically significant gray versus white matter differences

BACKGROUND: In accordance with ALARA, minimizing radiation exposure associated with voiding cystourethrograms (VCUG) is of critical importance. Advances in fluoroscopic technology might help achieve this goal. OBJECTIVE: To determine the efficacy of fluoroscopic image capture compared to conventional digital radiographic spot (DRS) images in voiding cystourethrograms (VCUG) for the evaluation of vesicoureteral reflux (VUR) in children. MATERIALS AND METHODS: The study was a retrospective review of 65 VCUG examinations (130 kidney/ureter units). Each examination consisted of fluoroscopically captured spot (FCS) images and the corresponding DRS images. Each set of images was evaluated by three pediatric radiologists for the diagnosis of VUR for a total of 390 kidney/ureter units reviewed. Using the DRS image set as the reference standard, the efficacy of the FCS images for diagnosing reflux was determined. RESULTS: The diagnostic accuracy of the FCS images in terms of the binary characterization of reflux as negative or positive was 97.2% (379/390). The sensitivity of the FCS images was 92.6% (88/95); the specificity of the FCS images was 98.6% (291/295). CONCLUSION: Fluoroscopically captured images are adequate in documenting absence of VUR on VCUG examinations, obviating the need for radiographic spot images and resulting in reduction in radiation exposure

OBJECTIVE: The purpose of this study was to evaluate the usefulness of MRI of the breast in cases in which mammographic or sonographic findings are inconclusive. MATERIALS AND METHODS: We retrospectively reviewed images from 115 MRI examinations of the breast performed from 1999 to 2005 for the indication of problem-solving for inconclusive findings on a mammogram. Forty-eight of the 115 women (41.8%) were at high risk. We discerned whether sonography or MRI was used as an adjunctive tool and correlated the findings with those in the pathology database. RESULTS: The equivocal findings most frequently leading to MRI were asymmetry and architectural distortion. No suspicious MRI correlate was found in 100 of 115 cases (87%). These cases were found stable at follow-up mammography or MRI after a mean of 34 months. Fifteen enhancing masses (13%) that corresponded to the mammographic abnormality were seen on MR images. All masses identified at MRI were accurately localized for biopsy, and six malignant lesions were identified. Four of six malignant tumors were seen in one mammographic view only; two were seen on second-look ultrasound images. MRI had a sensitivity of 100% and compared with mammography had significantly higher specificity (91.7% vs 80.7%, p = 0.029), positive predictive value (40% vs 8.7%, p = 0.032), and overall accuracy (92.2% vs 78.3%, p = 0.0052). Eighteen incidental lesions (15.7%) were detected at MRI, and all were subsequently found benign. CONCLUSION: We found breast MRI to be a useful adjunctive tool when findings at conventional imaging were equivocal. Strict patient selection criteria should be used because of the high frequency of incidental lesions seen on MR images

OBJECTIVE: The purpose of this study was to compare, with histopathologic examination of the liver explant as the reference standard, diffusion-weighted MRI with contrast-enhanced subtraction MRI in the assessment of necrosis of hepatocellular carcinoma (HCC) after trans arterial chemoembolization (TACE). MATERIALS AND METHODS: The cases of 21 patients with HCC who underwent MRI after TACE were evaluated. Two independent observers calculated the apparent diffusion coefficient (ADC) of HCC and measured percentage tumor necrosis on subtraction images. The ADCs of necrotic and viable tumor tissues were compared. ADC and percentage necrosis on subtraction images were correlated with percentage necrosis found at pathologic examination. Receiver operating characteristics analysis was performed on the diagnosis of complete tumor necrosis. RESULTS: Twenty-eight HCCs (mean diameter, 2.3 cm) were evaluated. There were significant differences between the ADC of viable tissue and that of necrotic tumor tissue (1.33 +/- 0.41 vs 2.04 +/- 0.38 x 10(-3) mm(2)/s, p < 0.0001). There was significant moderate correlation between ADC and the pathologic finding of percentage necrosis (r = 0.64, p < 0.001) and significant strong correlation between subtraction image and pathologic percentage necrosis (r = 0.89-0.91, depending on the phase; p < 0.001). In the diagnosis of complete tumor necrosis, ADC had an area under the curve, sensitivity, and specificity of 0.85, 75%, and 87.5% compared with 0.82-0.89, 100%, and 58.3-79.1% for subtraction imaging (p > 0.5 between ADC and subtraction imaging). CONCLUSION: Compared with diffusion-weighted imaging, contrast-enhanced MRI with subtraction technique had more significant correlation with the histopathologic findings in the evaluation of necrosis of HCC after TACE. There was no difference, however, between the two methods in diagnosis of complete tumor necrosis

PURPOSE: This study tested the hypothesis that the type of dose fractionation regimen determines the ability of radiotherapy to synergize with anti-CTLA-4 antibody. EXPERIMENTAL DESIGN: TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice at two separate sites, defined as a 'primary' site that was irradiated and a 'secondary' site outside the radiotherapy field. When both tumors were palpable, mice were randomly assigned to eight groups receiving no radiotherapy or three distinct regimens of radiotherapy (20 Gy x 1, 8 Gy x 3, or 6 Gy x 5 fractions in consecutive days) in combination or not with 9H10 monoclonal antibody against CTLA-4. Mice were followed for tumor growth/regression. Similar experiments were conducted in the MCA38 mouse colon carcinoma model. RESULTS: In either of the two models tested, treatment with 9H10 alone had no detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors but had no effect on the secondary tumors outside the radiation field. Conversely, the combination of 9H10 and either fractionated radiotherapy regimens achieved enhanced tumor response at the primary site (P < 0.0001). Moreover, an abscopal effect, defined as a significant growth inhibition of the tumor outside the field, occurred only in mice treated with the combination of 9H10 and fractionated radiotherapy (P < 0.01). The frequency of CD8+ T cells showing tumor-specific IFN-gamma production was proportional to the inhibition of the secondary tumor. CONCLUSIONS: Fractionated but not single-dose radiotherapy induces an abscopal effect when in combination with anti-CTLA-4 antibody in two preclinical carcinoma models

OBJECTIVE: Bilateral sequential cochlear implantation outcomes are dependent on many different factors. Newer technology in the second implanted ear may also contribute to outcome. This study examines the effect of cochlear implant technology on speech recognition outcomes in a population of adult patients who have undergone bilateral sequential implantation using different technologies in each ear. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Twenty adults who underwent bilateral sequential cochlear implantation with different technologies and processing strategies in each ear were patients for this study. Control Group A included patients (n = 8) who were simultaneously implanted, and Control Group B (n = 3) were patients who were sequentially implanted with the same technology. INTERVENTION: Bilateral sequential cochlear implantation. OUTCOME MEASURES: The outcome measure was the Consonant-Nucleus-Consonant monosyllabic word test administered in each implanted ear and in the binaural condition before and 1 year after operation. A multivariate analysis was performed to account for factors including duration of deafness, length of device usage, and severity of deafness. RESULTS: There was significant improvement from before to 1 year after the operation in word scores for the individual ears and in the binaural condition for all groups. All patients were consistent users of both devices, and the use of different technology in the second implanted ear did not affect the patients' ability to benefit from bilateral implantation despite the use of different devices and processing strategies. CONCLUSION: Bilateral sequential implantation with newer and/or differing technology in the second implanted ear did not reduce the benefits of bilateral stimulation and should not be considered a deterrent to second-sided implantation