Faculty Bibliography

Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. The purpose of this study was to prospectively evaluate sensitivity and specificity of various estimated perfusion parameters at three-dimensional (3D) perfusion magnetic resonance (MR) imaging of the liver in the diagnosis of advanced liver fibrosis (stage >or= 3), with histologic analysis, liver function tests, or MR imaging as the reference standard. Whole-liver 3D perfusion MR imaging was performed in 27 patients (17 men, 10 women; mean age, 55 years) after dynamic injection of 8-10 mL of gadopentetate dimeglumine. The following estimated perfusion parameters were measured with a dual-input single-compartment model: absolute arterial blood flow (F(a)), absolute portal venous blood flow (F(p)), absolute total liver blood flow (F(t)) (F(t) = F(a) + F(p)), arterial fraction (ART), portal venous fraction (PV), distribution volume (DV), and mean transit time (MTT) of gadopentetate dimeglumine. Patients were assigned to two groups (those with fibrosis stage <or= 2 and those with fibrosis stage >or= 3), and the nonparametric Mann-Whitney test was used to compare F(a), F(p), F(t), ART, PV, DV, and MTT between groups. Receiver operating characteristic curve analysis was used to assess the utility of perfusion estimates as predictors of advanced liver fibrosis. There were significant differences for all perfusion MR imaging-estimated parameters except F(p) and F(t). There was an increase in F(a), ART, DV, and MTT and a decrease in PV in patients with advanced fibrosis compared with those without advanced fibrosis. DV had the best performance, with an area under the receiver operating characteristic curve of 0.824, a sensitivity of 76.9% (95% confidence interval: 46.2%, 94.7%), and a specificity of 78.5% (95% confidence interval: 49.2%, 95.1%) in the prediction of advanced fibrosis

A three-compartment model is proposed for analyzing magnetic resonance renography (MRR) and computed tomography renography (CTR) data to derive clinically useful parameters such as glomerular filtration rate (GFR) and renal plasma flow (RPF). The model fits the convolution of the measured input and the predefined impulse retention functions to the measured tissue curves. A MRR study of 10 patients showed that relative root mean square errors by the model were significantly lower than errors for a previously reported three-compartmental model (11.6% +/- 4.9 vs 15.5% +/- 4.1; P < 0.001). GFR estimates correlated well with reference values by (99m)Tc-DTPA scintigraphy (correlation coefficient r = 0.82), and for RPF, r = 0.80. Parameter-sensitivity analysis and Monte Carlo simulation indicated that model parameters could be reliably identified. When the model was applied to CTR in five pigs, expected increases in RPF and GFR due to acetylcholine were detected with greater consistency than with the previous model. These results support the reliability and validity of the new model in computing GFR, RPF, and renal mean transit times from MR and CT data

PURPOSE: To examine CMRglc measures and corresponding glucose transport (K (1) and k (2)) and phosphorylation (k (3)) rates in the medial temporal lobe (MTL, comprising the hippocampus and amygdala) and posterior cingulate cortex (PCC) in mild Alzheimer's disease (AD). METHODS: Dynamic FDG PET with arterial blood sampling was performed in seven mild AD patients (age 68 +/- 8 years, four females, median MMSE 23) and six normal (NL) elderly (age 69 +/- 9 years, three females, median MMSE 30). Absolute CMRglc (mumol/100 g/min) was calculated from MRI-defined regions of interest using multiparametric analysis with individually fitted kinetic rate constants, Gjedde-Patlak plot, and Sokoloff's autoradiographic method with population-based rate constants. Relative ROI/pons CMRglc (unitless) was also examined. RESULTS: With all methods, AD patients showed significant CMRglc reductions in the hippocampus and PCC, and a trend towards reduced parietotemporal CMRglc, as compared with NL. Significant k (3) reductions were found in the hippocampus, PCC and amygdala. K (1) reductions were restricted to the hippocampus. Relative CMRglc had the largest effect sizes in separating AD from NL. However, the magnitude of CMRglc reductions was 1.2- to 1.9-fold greater with absolute than with relative measures. CONCLUSION: CMRglc reductions are most prominent in the MTL and PCC in mild AD, as detected with both absolute and relative CMRglc measures. Results are discussed in terms of clinical and pharmaceutical applicability

A method for calculating contrast agent concentration from MR signal intensity (SI) was developed and validated for T(1)-weighted MR renography (MRR) studies. This method is based on reference measurements of SI and relaxation time T(1) in a Gd-DTPA-doped water phantom. The same form of SI vs. T(1) dependence was observed in human tissues. Contrast concentrations calculated by the proposed method showed no bias between 0 and 1 mM, and agreed better with the reference values derived from direct T(1) measurements than the concentrations calculated using the relative signal method. Phantom-based conversion was used to determine the contrast concentrations in kidney tissues of nine patients who underwent dynamic Gd-DTPA-enhanced 3D MRR at 1.5T and (99m)Tc-DTPA radionuclide renography (RR). The concentrations of both contrast agents were found to be close in magnitude and showed similar uptake and washout behavior. As shown by Monte Carlo simulations, errors in concentration due to SI noise were below 10% for SNR = 20, while a 10% error in precontrast T(1) values resulted in a 12-17% error for concentrations between 0.1 and 1 mM. The proposed method is expected to be particularly useful for assessing regions with highly concentrated contrast

The accuracy and precision of an automated graph-cuts (GC) segmentation technique for dynamic contrast-enhanced (DCE) 3D MR renography (MRR) was analyzed using 18 simulated and 22 clinical datasets. For clinical data, the error was 7.2 +/- 6.1 cm(3) for the cortex and 6.5 +/- 4.6 cm(3) for the medulla. The precision of segmentation was 7.1 +/- 4.2 cm(3) for the cortex and 7.2 +/- 2.4 cm(3) for the medulla. Compartmental modeling of kidney function in 22 kidneys yielded a renal plasma flow (RPF) error of 7.5% +/- 4.5% and single-kidney GFR error of 13.5% +/- 8.8%. The precision was 9.7% +/- 6.4% for RPF and 14.8% +/- 11.9% for GFR. It took 21 min to segment one kidney using GC, compared to 2.5 hr for manual segmentation. The accuracy and precision in RPF and GFR appear acceptable for clinical use. With expedited image processing, DCE 3D MRR has the potential to expand our knowledge of renal function in individual kidneys and to help diagnose renal insufficiency in a safe and noninvasive manner

OBJECTIVE: The aim of this study was to determine the benefit of lower extremity CT venography (CTV) with pulmonary CT angiography (CTA) for diagnosing thromboembolic (TE) disease. SUBJECTS AND METHODS: Reports of all CTAs and CTVs over a 3-year interval (Group I) and CTAs, CTVs, and lower extremity Doppler ultrasounds (US) over a 1 1/2-year subset (Group II) were reviewed. Patient population was inpatients and emergency department patients who were assessed for pulmonary embolism (PE) and deep venous thrombosis (DVT) at a tertiary care hospital. Reported results for CTA or CTV were categorized as positive (CTA(P), CTV(P)), negative (CTA(N), CTV(N)), or indeterminate for PE or DVT. When CTV and US results were discrepant, medical records were reviewed for clinical management. Additional benefit of CTV was assessed by chi-square analysis. RESULTS: In Group I, 737 (81.1%) of 909 CTAs from combined CTA/CTV studies were negative. The diagnosis rate of TE disease increased from 13.0% to 17.3% with the addition of CTV(P)s (P=.01). Of the 119 cases in Group II undergoing combined CTA, CTV, and US, CTV and US were both positive in eight and both negative in 88. Of the seven discordant CTVs and USs with clinical follow-up, five CTVs were positive while USs were negative, three of which were treated clinically for TE disease, while two were considered falsely positive. As CTA also proved positive in one of the three, CTV therefore affected management in two of these five cases and increased the rate of thromboembolism diagnosis from 21.0% to 22.6%; however, this was not significant (P>.05). Two CTV(N)s were managed as false negatives. CONCLUSIONS: The combined use of CTA and CTV significantly increases the rate of TE disease over CTA alone. In cases in which ultrasound is performed, however, there is no significant advantage to performing combined CTA/CTV studies

The purpose of this study was to determine the accuracy and sources of error in estimating single-kidney glomerular filtration rate (GFR) derived from low-dose gadolinium-enhanced T1-weighted MR renography. To analyze imaging data, MR signal intensity curves were converted to concentration vs. time curves, and a three-compartment, six-parameter model of the vascular-nephron system was used to analyze measured aortic, cortical, and medullary enhancement curves. Reliability of the parameter estimates was evaluated by sensitivity analysis and by Monte Carlo analyses of model solutions to which random noise had been added. The dominant sensitivity of the medullary enhancement curve to GFR 1-4 min after tracer injection was supported by a low coefficient of variation in model-fit GFR values (4%) when measured data were subjected to 5% noise. These analyses also showed the minimal effects of bolus dispersion in the aorta on parameter reliability. Single-kidney GFR from MR renography analyzed by the three-compartment model (4.0-71.4 ml/min) agreed well with reference measurements from (99m)Tc-DTPA clearance and scintigraphy (r = 0.84, P < 0.001). Bland-Altman analysis showed an average difference of 11.9 ml/min (95% confidence interval = 5.8-17.9 ml/min) between model and reference values. We conclude that a nephron-based multicompartmental model can be used to derive clinically useful estimates of single-kidney GFR from low-dose MR renography.

BACKGROUND AND PURPOSE: More than 85% of brain traumas are classified as 'mild'; MR imaging findings are minimal if any and do not correspond to clinical symptoms. Our goal, therefore, was to quantify the global decline of the neuronal marker N-acetylaspartate (NAA), as well as gray (GM) and white matter (WM) atrophy after mild traumatic brain injury (mTBI). MATERIALS AND METHODS: Twenty patients (11 male, 9 female; age range, 19-57 years; median, 35 years) with mTBI (Glasgow Coma Scale score 13-15 with loss of consciousness for at least 30 seconds) and 19 age- and sex-matched control subjects were studied. Seven patients were studied within 9 days of TBI; the other 13 ranged from 1.2 months to 31.5 years (average and median of 4.6 and 1.7 years, respectively) after injury. Whole-brain NAA (WBNAA) concentration was obtained in all subjects with nonlocalizing proton MR spectroscopy. Brain volume and GM and WM fractions were segmented from T1-weighted MR imaging and normalized to the total intracranial volume, suitable for intersubject comparisons. The data were analyzed with least squares regression. RESULTS: Patients with mTBI exhibited, on average, a 12% WBNAA deficit that increased with age, compared with the control subjects (p<.05). Adjusted for age effects, patients also suffered both global atrophy (-1.09%/year; P=.029) and GM atrophy (-0.89%/year; P=.042). Patients with and without visible MR imaging pathology, typically punctate foci of suspected shearing injury, were indistinguishable in both atrophy and WBNAA. CONCLUSION: WBNAA detected neuronal/axonal injury beyond the minimal focal MR-visible lesions in mTBI. Combined with GM atrophy, the findings may provide further, noninvasive insight into the nature and progression of mTBI

PURPOSE: To investigate whether the loss of corticomedullary differentiation (CMD) on T1-weighted MR images due to renal insufficiency can be attributed to changes in T1 values of the cortex, medulla, or both. MATERIALS AND METHODS: Study subjects included 10 patients (serum creatinine range 0.6-3.0 mg/dL) referred for suspected renovascular disease who underwent 99mTc-diethylene triamine pentaacetic acid (DTPA) renography to determine single kidney glomerular filtration rate (SKGFR) and same-day MRI, which included T1 measurements and unenhanced T1-weighted gradient echo imaging. Corticomedullary differentiation on T1-weighted images was assessed qualitatively and quantitatively. RESULTS: SKGFR values ranged from 3.5 to 89.4 mL/minute based on radionuclide studies. T1 relaxation times of the medulla exceeded those of renal cortex by 147.9+/-176.0 msec (mean+/-standard deviation [SD]). Regression analysis showed a negative correlation between cortex T1 and SKGFR (r=-0.5; P=0.03), whereas there was no significant correlation between medullary T1 and SKGFR. The difference between medullary and cortical T1s correlated significantly with SKGFR (r=0.58; P<0.01). In all five kidneys with a corticomedullary contrast-to-noise ratio (CNR)<5.0 on T1-weighted images, SKGFR was less than 20 mL/minute. CONCLUSION: In our subject population, loss of CMD with decreasing SKGFR can be attributed primarily to an increased T1 relaxation time of the cortex. Medullary T1 values vary but do not appear to correlate with degree of renal insufficiency.

It is widely believed that the path to early and effective treatment for Alzheimer's disease (AD) requires the development of early diagnostic markers that are both sensitive and specific. To this aim, using longitudinal study designs, we and others have examined magnetic resonance imaging (MRI), 2-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG/PET), and cerebrospinal fluid (CSF) biomarkers in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI). Such investigations have led to the often replicated findings that structural evidence of hippocampal atrophy as determined by MRI, as well as metabolic evidence from FDG-PET scan of hippocampal damage, predicts the conversion from MCI to AD. In this article we present a growing body of evidence of even earlier diagnosis. Brain pathology can be detected in NL subjects and used to predict future transition to MCI. This prediction is enabled by examinations revealing reduced glucose metabolism in the hippocampal formation (hippocampus and entorhinal cortex [EC]) as well as by the rate of medial temporal lobe atrophy as determined by MRI. However, neither regional atrophy nor glucose metabolism reductions are specific for AD. These measures provide secondary not primary evidence for AD. Consequently, we will also summarize recent efforts to improve the diagnostic specificity by combining imaging with CSF biomarkers and most recently by evaluating amyloid imaging using PET. We conclude that the combined use of conventional imaging, that is MRI or FDG-PET, with selected CSF biomarkers incrementally contributes to the early and specific diagnosis of AD. Moreover, selected combinations of imaging and CSF biomarkers measures are of importance in monitoring the course of AD and thus relevant to evaluating clinical trials