Faculty Bibliography

We hypothesize that normal aging implies neuronal durability, reflected by age-independent concentrations of their marker-the amino acid derivative N-acetylaspartate (NAA). To test this, we obtained the whole-brain and whole-head N-acetylaspartate concentrations (WBNAA and WHNAA) with proton magnetic resonance (MR) spectroscopy; and the fractional brain parenchyma volume (fBPV)-a metric of atrophy, by segmenting the magnetic resonance image (MRI) from 42 (18 male) healthy young (31.9 +/- 5.8 years old) and 100 (64 male, 72.6 +/- 7.3 years old) cognitively normal elderly. The 12.8 +/- 1.9 mM WBNAA of the young was not significantly different from the 13.1 +/- 3.1 mM in the elderly (p > 0.05). In contrast, both fBPV (87.3 +/- 4.7% vs. 74.8 +/- 4.8%) and WHNAA (11.1 +/- 1.7 mM vs. 9.8 +/- 2.4 mM) were significantly higher in the young (approximately 14%; p < 0.0001 for both). The similarity in mean WBNAA between 2 cohorts 4 decades of normal aging apart suggests that neuronal integrity is maintained across the lifespan. Clinically, WBNAA could be used as a marker for normal (hence, also abnormal) brain aging. In contrast, WHNAA and fBPV seem age-related suggesting that brain atrophy may occur without compromising the remaining tissue.

OBJECTIVE: The purpose of this study is to assess the accuracy of MRI quantification of glenoid bone loss and to compare the diagnostic accuracy of MRI to CT in the measurement of glenoid bone loss. MATERIALS AND METHODS: MRI, CT, and 3D CT examinations of 18 cadaveric glenoids were obtained after the creation of defects along the anterior and anteroinferior glenoid. The defects were measured by three readers separately and blindly using the circle method. These measurements were compared with measurements made on digital photographic images of the cadaveric glenoids. Paired sample Student t tests were used to compare the imaging modalities. Concordance correlation coefficients were also calculated to measure interobserver agreement. RESULTS: Our data show that MRI could be used to accurately measure glenoid bone loss with a small margin of error (mean, 3.44%; range, 2.06-5.94%) in estimated percentage loss. MRI accuracy was similar to that of both CT and 3D CT for glenoid loss measurements in our study for the readers familiar with the circle method, with 1.3% as the maximum expected difference in accuracy of the percentage bone loss between the different modalities (95% confidence). CONCLUSION: Glenoid bone loss can be accurately measured on MRI using the circle method. The MRI quantification of glenoid bone loss compares favorably to measurements obtained using 3D CT and CT. The accuracy of the measurements correlates with the level of training, and a learning curve is expected before mastering this technique.

OBJECTIVE: The purpose of this study was to evaluate the utility of multiparametric MRI in localization of the index lesion of prostate cancer. MATERIALS AND METHODS: Fifty-one patients who underwent 3-T MRI of the prostate with a pelvic phased-array coil that included T2-weighted, diffusion-weighted, and dynamic contrast-enhanced sequences before prostatectomy were included. Six radiologists assessed all images to identify the lesion most suspicious of being the index lesion, which was localized to one of 18 regions. A uropathologist using the same 18-region scheme reviewed the prostatectomy slides to localize the index lesion. MRI performance was assessed by requiring either an exact match or an approximate match (discrepancy of up to one region) between the MRI and pathologic findings in terms of assigned region. RESULTS: The pathologist identified an index lesion in 49 of 51 patients. In exact-match analysis, the average sensitivity was 60.2% (range, 51.0-63.3%), and the average positive predictive value (PPV) was 65.3% (range, 61.2-69.4%). In approximate-match analysis, the average sensitivity was 75.9% (range, 65.3-69.6%), and the average PPV was 82.6% (range, 79.2-91.4%). The sensitivity was higher for index lesions with a Gleason score greater than 6 in exact-match (74.8% vs 15.3%, p < 0.001) and approximate-match (88.7% vs 36.1%, p = < 0.001) analyses and for index lesions measuring at least 1 cm in approximate-match analysis (80.3% vs 58.3%, p = 0.016). In exact-match analysis, 30.0%, 44.9%, and 79.1% of abnormalities found with one, two, and three MRI parameters represented the index lesion (p < 0.001). CONCLUSION: The sensitivity and PPV of multiparametric MRI for index lesion localization were moderate, although they improved in the setting of more aggressive pathologic features and a greater number of abnormal MRI parameters, respectively.

OBJECTIVE: The purpose of this study was to assess the effect of hepatic iron deposition on apparent diffusion coefficient (ADC) values measured with single-shot echo-planar imaging (EPI) diffusion-weighted MRI (DWI) in patients with liver cirrhosis and in vitro. MATERIALS AND METHODS: Fifty-two patients with liver cirrhosis who underwent breath-hold single-shot EPI DWI at 1.5 T before liver transplantation were retrospectively assessed. Estimated signal-to-noise ratio (SNR(est)) and ADC were measured in the right hepatic lobe (for b values of 50 and 500 s/mm(2)). SNR(est) and ADC were compared between patients stratified by pathologic iron grade using the Mann-Whitney test. Hepatic ADC values were correlated to T2(*) values using the Spearman correlation test in a subset of patients. In addition, a phantom consisting of solutions of varying iron concentrations was imaged with single-shot EPI DWI and T2(*) imaging, and iron concentration was correlated with ADC and T2(*). RESULTS: In phantoms, there was a decrease in ADC and T2(*) with increasing iron concentration (r = -0.95 and -0.92, respectively; p < 0.05). Patients with hepatic siderosis had significantly lower SNR(est) and ADC compared with patients without siderosis (p < 0.0001). SNR(est) at b = 50 s/mm(2) and b = 500 s/mm(2) and ADC had a significant negative correlation with pathologic iron grade (r = -0.67 to 0.77, p < 0.0001). There was a significant correlation between liver T2(*) and ADC (r = 0.83, p < 0.0001). CONCLUSION: Hepatic siderosis lowers liver ADC and should be taken into account when using ADC for diagnosing liver cirrhosis.

A promising strategy for cancer immunotherapy is to disrupt key pathways regulating immune tolerance, such as cytotoxic T lymphocyte-associated protein 4 (CTLA-4). However, the determinants of response to anti-CTLA-4 mAb treatment remain incompletely understood. In murine models, anti-CTLA-4 mAbs alone fail to induce effective immune responses to poorly immunogenic tumors but are successful when combined with additional interventions, including local ionizing radiation (IR) therapy. We employed an established model based on control of a mouse carcinoma cell line to study endogenous tumor-infiltrating CD8+ T lymphocytes (TILs) following treatment with the anti-CTLA-4 mAb 9H10. Alone, 9H10 monotherapy reversed the arrest of TILs with carcinoma cells in vivo. In contrast, the combination of 9H10 and IR restored MHC class I-dependent arrest. After implantation, the carcinoma cells had reduced expression of retinoic acid early inducible-1 (RAE-1), a ligand for natural killer cell group 2D (NKG2D) receptor. We found that RAE-1 expression was induced by IR in vivo and that anti-NKG2D mAb blocked the TIL arrest induced by IR/9H10 combination therapy. These results demonstrate that anti-CTLA-4 mAb therapy induces motility of TIL and that NKG2D ligation offsets this effect to enhance TILs arrest and antitumor activity.

Conventional imaging is unable to detect damage that accounts for permanent cognitive impairment in patients with mild traumatic brain injury (MTBI). While diffusion tensor imaging (DTI) can help to detect diffuse axonal injury (DAI), it is a limited indicator of tissue complexity. It has also been suggested that the thalamus may play an important role in the development of clinical sequelae in MTBI. The purpose of this study was to determine if diffusional kurtosis imaging (DKI), a novel quantitative magnetic resonance imaging (MRI) technique, can provide early detection of damage in the thalamus and white matter (WM) of MTBI patients and if thalamic injury is associated with cognitive impairment. Twenty-two MTBI patients and 14 controls underwent MRI and neuropsychological testing. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) were measured in the thalamus and several WM regions classically identified with DAI. Compared to controls, patients examined within one year after injury exhibited variously altered DTI and DKI derived measures in the thalamus and the internal capsule while, in addition to these regions, patients examined more than one year after injury also showed similar differences in the splenium of the corpus callosum and the centrum semiovale. Cognitive impairment was correlated to MK in the thalamus and the internal capsule. These findings suggest that combined use of DTI and DKI provides a more sensitive tool for identifying brain injury. In addition, MK in the thalamus might be useful for early prediction of permanent brain damage and cognitive outcome

OBJECTIVE: Total renal volume and changes in kidney volume are markers of disease progression in autosomal-dominant polycystic kidney disease (ADPKD) but are not used in clinical practice in part because of the complexity of manual measurements. This study aims to assess the intra- and interobserver reproducibility of a semiautomated renal volumetric algorithm using fluid-sensitive MRI pulse sequences. SUBJECTS AND METHODS: Renal volumes of 17 patients with ADPKD were segmented from high-resolution coronal HASTE and true fast imaging with steady-state precession (FISP) MR acquisitions. Measurements performed independently by four readers were repeated, typically after 7 days. Intraobserver agreement indexes were calculated for total kidney volume for each patient. Interobserver agreement indexes were obtained for the six paired combinations of readers as well as for two readers after rigorous formalized training. Pearson and concordance correlation coefficients, coefficients of variation (CVs), and 95% limits of agreement were determined. RESULTS: The HASTE and true FISP sequences performed similarly with a median intraobserver agreement of greater than 98.1% and a CV of less than 2.4% across all readers. The median interobserver agreement was greater than 95.2% and the CV was less than 7.1%, across all reader pairs. Reader training further lowered interobserver CV. The mean total kidney volume was 1420 mL (range, 331-3782 mL) for HASTE imaging and 1445 mL (range, 301-3714 mL) for true FISP imaging, with mean image processing times per patient of 43 and 28 minutes, respectively. CONCLUSION: This semiautomated MR volumetric algorithm provided excellent intraobserver and very good interobserver reproducibility using fluid-sensitive pulse sequences that emphasize cyst conspicuity.

Abstract Background: Early identification of coronary artery disease (CAD) among symptomatic women is critical given their worse outcomes as compared to men. We evaluated the value of the Morise score, a simple clinical risk score, for the assessment for CAD as determined by computed tomography coronary angiography (CTCA) and compared it to the Diamond-Forrester risk assessment. Methods: One hundred forty women (mean age, 64+/-11 years) with chest pain syndromes and no known CAD referred for CTCA were analyzed. Patients were risk stratified for likelihood of CAD by Morise and Diamond-Forrester scores. The presence and degree of CAD were determined by CTCA and classified as normal, nonobstructive (<50% stenosis), or obstructive (>50% stenosis). Total coronary calcium was calculated based on Agatston scores. Results: When risk was assessed by Morise vs. Diamond-Forrester, 5% vs. 7% of women were stratified as low, 41% vs. 82% as intermediate, and 54% vs. 11% as high risk for CAD, respectively. CAD was present in 95 (68%) patients; 22 (16%) had obstructive CAD, and 73 (52%) had nonobstructive CAD. Morise scores significantly correlated with calcium scores (p<0.001) as well as the presence and degree of CAD (p<0.0001). Morise scores also demonstrated significantly higher accuracy (66% vs. 48%, p<0.005) and higher sensitivity (56% vs. 16%, p<0.001) but lower specificity (82% vs. 97%, p<0.05) when compared to Diamond-Forrester risk assessment. Conclusions: The Morise score performed better than Diamond-Forrester for CAD risk assessment, which highlights the importance and power of a simple history and physical examination in determining women at risk for CAD.

OBJECTIVES To assess the cross-sectional area and angle of the internal nasal valve more accurately by reformatting computed tomography (CT) scans of the nasal airway according to a more appropriate orientation than scans traditionally sectioned in the coronal plane and then to compare the results with clinical data on the nasal valve obtained from physical examination. METHODS We performed a retrospective review of the medical records of 24 rhinoplasty patients treated at a private practice facial plastic surgery office affiliated with a tertiary care university hospital. The patients had fine-cut (0.75-mm section) CT scans ordered for nasal airway obstruction or nasal valve compromise at the same institution. These patients were evaluated from January 1, 2000, through December 31, 2010. The previously acquired CT scans were reformatted to obtain sections through the internal nasal valve at a more appropriate orientation. The internal nasal valve cross-sectional area and valve angle were measured through a standardized section (1 cut immediately anterior to the head of the inferior turbinate) from the reformatted scans. The cross-sectional area was also measured through the same point on the traditionally oriented CT scan, and the values were compared. The results from each patient's scan were compared with data from the patient's medical record and analyzed against the patient's preoperative modified Cottle examination findings. RESULTS The CT scans oriented in the reformatted plane through the internal nasal valve provided a narrower valve angle than the traditionally oriented CT scans and more closely approximated the hypothesized true value of the internal nasal valve of 10 degrees to 15 degrees (P < .001). In a comparison of the same-side internal nasal valve angle and cross-sectional nasal valve area between the 2 different CT scan orientations, a statistically significant difference in the internal nasal valve angles between the 2 scan orientations was discovered, but this finding did not reach significance when distinguishing the nasal valve cross-sectional area. Finally, no correlation was found with regard to the preoperative modified Cottle maneuver scores for the internal nasal valve angle and cross-sectional valve area values in either scan orientation. CONCLUSIONS Precise preoperative evaluation of the internal nasal valve is critical to the workup for reconstruction or repair of problems that involve this area. Although tools such as acoustic rhinometry exist to evaluate the cross-sectional area of the nasal valve, many rhinoplasty surgeons do not have access to this expensive equipment. A CT scan with reformatting in the proper plane of the internal nasal valve can provide the surgeon with improved anatomical information to assess that region. With this in mind, however, the surgeon should always perform a thorough preoperative physical examination and treat the patient and his or her symptoms, not the imaging studies, when considering a candidate for a surgical intervention.

OBJECTIVE: The purpose of this study is to retrospectively compare 1D, 2D, and 3D measurements on CT for detection of growth of solid renal masses on active surveillance. MATERIALS AND METHODS: Forty solid renal masses measuring at least 1 cm in patients who underwent two CT studies at least 3 months apart were included. Two radiologists independently assessed the studies for interval growth using gestalt visual assessment and 1D, 2D, and 3D measurements. Prospective reports were also evaluated for indications of growth. The summation-of-areas technique was used to calculate volumes of lesions, which served as reference standard in determination of growth. Logistic regression analysis for correlated data was used to compare accuracy of methodologies for detection of lesion growth. Interreader agreement was assessed using kappa coefficients and intraclass correlation coefficients. RESULTS: The accuracy of gestalt visual, 1D, 2D, and 3D assessments for detection of interval growth was 72.5%, 70.0%, 82.5%, and 85% for reader 1 and 77.5%, 70.0%, 90.0%, and 95.0% for reader 2. These differences were significant or nearly significant (p = 0.003-0.054) for the greater accuracy of 2D or 3D measurements than for 1D measurements for reader 1 as well as the greater accuracy of 2D measurements than 1D measurements and 3D measurements than gestalt visual assessment or 1D measurements for reader 2. The accuracy of prospective reports for detection of growth was 65.0%. Reader agreement was fair for gestalt visual assessment (kappa = 0.31) and nearly perfect for 1D, 2D, and 3D measurements (intraclass correlation coefficient = 0.97-0.99). CONCLUSION: Our results show that 2D or 3D measurements may be preferable to 1D measurements on CT in assessment for growth of solid renal masses on active surveillance.