Faculty Bibliography

OBJECTIVE: To establish the progression of brain atrophy rates in patients with a known date of onset of Alzheimer disease (AD). METHODS: Each of 18 subjects had two high-resolution T1-weighted three-dimensional MRI examinations. The two MRIs were coregistered and the annual rate of brain tissue atrophy was derived both for the entire brain and regionally for the left and right medial temporal lobe (MTL). Time since onset (TSO) of AD, defined as the interval between the date of onset and the midpoint of MRI dates, ranged from -2.9 to 4.2 years. RESULTS: In patients with AD, TSO was a correlate of the atrophy rate for both the left MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial measurements were applied to a control group of 21 cognitively normal elderly subjects, MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. CONCLUSION: Increased annual atrophy rate in the medial temporal lobe is a potential diagnostic marker of the progression of Alzheimer disease

PURPOSE OF REVIEW: Current magnetic resonance imaging systems allow the visualization of normal and diseased kidney, with exquisite resolution of renal structures. Dynamic contrast magnetic resonance imaging has the potential, unique among all noninvasive modalities, to differentiate diseases that affect different portions of the vascular-nephron system. This article reviews the most important recently published studies in selected topics chosen because of their clinical relevance or potential for technical developments. RECENT FINDINGS: Magnetic resonance imaging is used increasingly to evaluate renal masses, the prenatal genitourinary system, urinary obstruction and infection, renal vasculature, and the kidneys of transplant donors and recipients. Dynamic contrast magnetic resonance renography based on gadolinium chelated to diethylenetriamine pentaacetic acid, a safe (non-nephrotoxic) paramagnetic agent, emerges as the functional renal imaging modality of choice. Both perfusion and filtration rates can be assessed in individual kidney. SUMMARY: Magnetic resonance imaging has the potential to provide a complete anatomic, physiologic, kidney-specific evaluation. With future advances in automated image analysis methods we can expect functional renal magnetic resonance imaging to play an influential role in management of renal disease

The main goal of our studies has been to use MRI, FDG-PET, and CSF biomarkers to identify in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI), the earliest clinically detectable evidence for brain changes due to Alzheimer's disease (AD). A second goal has been to describe the cross-sectional and longitudinal interrelationships amongst anatomical, CSF and cognition measures in these patient groups. It is now well known that MRI-determined hippocampal atrophy predicts the conversion from MCI to AD. In our summarized studies, we show that the conversion of NL subjects to MCI can also be predicted by reduced entorhinal cortex (EC) glucose metabolism, and by the rate of medial temporal lobe atrophy as determined by a semi-automated regional boundary shift analysis (BSA-R). However, whilst atrophy rates are predictive under research conditions, they are not specific for AD and cannot be used as primary evidence for AD. Consequently, we will also review our effort to improve the diagnostic specificity by evaluating the use of CSF biomarkers and to evaluate their performance in combination with neuroimaging. Neuropathology studies of normal ageing and MCI identify the hippocampal formation as an early locus of neuronal damage, tau protein pathology, elevated isoprostane levels, and deposition of amyloid beta 1-42 (Abeta42). Many CSF studies of MCI and AD report elevated T-tau levels (a marker of neuronal damage) and reduced Abeta42 levels (possibly due to increased plaque sequestration). However, CSF T-tau and Abeta42 level elevations may not be specific to AD. Elevated isoprostane levels are also reported in AD and MCI but these too are not specific for AD. Importantly, it has been recently observed that CSF levels of P-tau, tau hyperphosphorylated at threonine 231 (P-tau231) are uniquely elevated in AD and elevations found in MCI are useful in predicting the conversion to AD. In our current MCI studies, we are examining the hypothesis that elevations in P-tau231 are accurate and specific indicators of AD-related changes in brain and cognition. In cross-section and longitudinally, our results show that evaluations of the P-tau231 level are highly correlated with reductions in the MRI hippocampal volume and by using CSF and MRI measures together one improves the separation of NL and MCI. The data suggests that by combining MRI and CSF measures, an early (sensitive) and more specific diagnosis of AD is at hand. Numerous studies show that neither T-tau nor P-tauX (X refers to all hyper-phosphorylation site assays) levels are sensitive to the longitudinal progression of AD. The explanation for the failure to observe longitudinal changes is not known. One possibility is that brain-derived proteins are diluted in the CSF compartment. We recently used MRI to estimate ventricular CSF volume and demonstrated that an MRI-based adjustment for CSF volume dilution enables detection of a diagnostically useful longitudinal P-tau231 elevation. Curiously, our most recent data show that the CSF isoprostane level does show significant longitudinal elevations in MCI in the absence of dilution correction. In summary, we conclude that the combined use of MRI and CSF incrementally contributes to the early diagnosis of AD and to monitor the course of AD. The interim results also suggest that a panel of CSF biomarkers can provide measures both sensitive to longitudinal change as well as measures that lend specificity to the AD diagnosis.

We describe an open structure of permanently magnetized material for interventional magnetic resonance imaging of the brain. We transformed the ideal magnet, contained between two coaxial cones, into a practical device by a series of geometrical steps that minimize field perturbations. By taking advantage of the quasi-linear demagnetization characteristics of rare-earth materials, we could analyze the structure with an exact mathematical model. The magnet, built of material of remanence 1.38 T, generates a field of 0.45 T within its central gap 30 cm wide. Our numerical computations show a remarkable 0.25% field uniformity in the imaging region. The large opening makes the conical magnet suitable for interventional and surgical imaging

The demographics of aging identify an immediate need for the early diagnosis and development of dementia prevention strategies. Recent neuropathological studies have pointed to the early involvement of the hippocampus and entorhinal cortex in the progression of Alzheimer's disease in the brain. In particular, these studies have implicated tau-related pathology as an important cause of neuronal death. In addition, there is a large body of evidence showing that beta-amyloid, which has a predilection for the neocortex, is also involved early in the course of the disease and may also have toxic effects on cells. In vivo cerebrospinal fluid studies have shown that markers for these brain changes have a diagnostic value for Alzheimer's disease and that some measures also provide diagnostic specificity for Alzheimer's disease. Structural and metabolic imaging studies demonstrate brain changes in impaired and at-risk individuals. While currently available magnetic resonance and positron emission tomography techniques are not by themselves specific for the pathologic features of Alzheimer's disease, there are patterns of change that have been useful for the early diagnosis. As such, both prediction and longitudinal imaging studies demonstrate a capacity to recognize abnormalities that relate to future Alzheimer's disease and most recently to future mild cognitive impairment. This review highlights cross-sectional, prediction, and longitudinal magnetic resonance and positron emission tomography imaging studies and attempts to put into perspective their utility for the early diagnosis of Alzheimer's disease, and for their utility to provide diagnostic specificity. It is concluded that there is considerable promise for an early and specific diagnosis for Alzheimer's disease by combining information from imaging and biomarker modalities

MR imaging is the only noninvasive test that may provide a complete picture of renal status with minimal risk to the patient, simultaneously improving diagnosis and lowering costs. This article reviews several MR renography techniques, including approaches for quantifying renal perfusion and glomerular filtration rate. Also discussed are clinical applications for the diagnosis and follow-up of renovascular disease, hydronephrosis,and renal transplant dysfunction. The article concludes with an overview of technical problems and challenges facing MR renography

OBJECTIVE: The purpose of this study was to compare combined cine gradient-recalled echo MRI and MR angiography with conventional angiography in the evaluation of the pulmonary vascular supply in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries. MATERIALS AND METHODS: Eleven patients who underwent both MRI and conventional angiography were retrospectively reviewed. Contiguous 2D cine gradient-recalled echo images (TR range/TE, 30-80/4.8; flip angle, 20 degrees or 30 degrees ) and 3D MR angiographic images (TR range/TE range, 3.8-5.0/1.3-2.0; acquisition time, 13-32 sec) using gadopentetate meglumine (0.1-0.2 mmol/kg) were obtained. The presence, size, and course of the pulmonary arteries (main, right, left) and major aortopulmonary collateral arteries (>/= 5 mm) were determined. Presence of minor collateral arteries (< 5 mm) was also noted. Results were compared with findings at conventional angiography. RESULTS: MRI showed all main (n = 4) and branch (n = 17) pulmonary arteries found at conventional angiography and showed the pulmonary confluence in five of six cases. MRI showed all major aortic collaterals (n = 22) with a highly significant correlation between MRI and conventional angiography measurements (r = 0.84, p < 0.001 [95% confidence interval, -0.35 to 0.40]). One coronary artery collateral was not shown on MRI examination. At MRI, 12 of 14 major and four of seven minor brachiocephalic artery collaterals were shown. MRI showed more minor aortic collaterals than angiography (22 vs 18 vessels, respectively). CONCLUSION: Combined cine gradient-recalled echo MRI and MR angiography is a reliable method for imaging pulmonary vascular supply in patients with these disorders. Additional prospective studies comparing MRI and conventional angiography may determine whether routine preoperative conventional angiography is required

PURPOSE: To determine if medial temporal lobe (MTL) atrophy rate, assessed by using an automated procedure over the initial time interval of a 6-year, three-time-point longitudinal study, is predictive of future memory decline. MATERIALS AND METHODS: Healthy elderly subjects (age, >60 years) were administered a comprehensive battery of neuropsychometric tests and underwent magnetic resonance (MR) imaging at baseline and two or more follow-up examinations. The rate of brain atrophy between the baseline and first follow-up examinations was assessed by using an automated procedure that included spatial coregistration of the two images and regional brain boundary shift analysis. At final observation, the 45 subjects were separated into a group of those who did and a group of those who did not show objective evidence of cognitive decline. A forward stepwise logistic regression model was used to identify variables that predicted decline. RESULTS: Thirty-two subjects remained healthy, and 13 showed cognitive decline. Among subjects who showed cognitive decline, six declined after the second observation. MTL atrophy rate, through its interactions with sex and age, was the most significant predictor of decline. The overall accuracy of prediction was 89% (in 40 of 45 subjects), with 91% specificity (in 29 of 32 subjects) and 85% sensitivity (in 11 of 13 subjects). CONCLUSION: Among healthy elderly individuals, increased MTL atrophy rate appears to be predictive of future memory decline