A novel approach for quantifying cerebral blood flow (CBF) is proposed that combines the bookend technique of calculating cerebral perfusion with an automatic postprocessing algorithm. The reproducibility of the quantitative CBF (qCBF) measurement in healthy controls (N ‫؍‬ 8) showed a higher intraclass correlation coefficient (ICC) and lower coefficient of variation (COV) when calculated with automatic analysis (ICC/COV ‫؍‬ 0.90/0.09) than when compared to conventional manual analysis (ICC/COV ‫؍‬ 0.58/0.19). Also, the reproducibility in patients (N ‫؍‬ 25) was successfully evaluated with the automatic analysis (ICC/COV ‫؍‬ 0.81/0.14). In 175 consecutive clinical scans, we found 3.0% and 7.4% of qCBF decrease per decade in white matter (WM) (21.5 ؎ 6.66 ml/100 g-min) and gray matter (GM) (49.6 ؎ 16.2 ml/100 g-min), respectively. Cerebral blood volume (CBV) showed a significant 3.7% decrease per decade in GM (3.00 ؎ 0.94 ml/100 g) but not in WM (1.69 ؎ 0.40 ml/100 g). Bolus tracking cerebral perfusion has been shown to reflect the underlying pathophysiology in a variety of diseases including cerebrovascular occlusive disease, stroke, central nervous system tumors, and potentially Alzheimer's disease (1-5). Parametric images of cerebral perfusion are calculated by analyzing the tracer kinetics of a known tracer, whether it is: radio-labeled water in positron emission tomography (PET), iodinated contrast agent in computed tomography (CT), spin-labeled water in arterial spin labeling, or a paramagnetic contrast agent in dynamic susceptibility contrast (DSC) MR imaging. While radiolabeled PET is the standard of reference for quantification of cerebral perfusion, the necessity of a cyclotron limits its availability. CT has the potential to quantify perfusion; however, iodinated contrast and large doses of radiation are required. This is particularly problematic for frequent follow-up or in certain populations, such as pediatric patients in which the radiation dose should be minimized MR-based parametric images of relative cerebral blood flow (CBF) and cerebral blood volume (CBV) images using DSC analysis are commonly used to assess changes in cerebral perfusion. The development of quantitative MRbased perfusion (i.e., in ml/100 g-min) has been identified by the American Heart Association as a priority for treatment of acute stroke (6). However, quantitative perfusion MR with DSC analysis has been elusive and challenging (7-10).One approach to quantification of perfusion using MRI has been to assume a population-averaged value for normal white matter (WM) and determine quantitative values relative to "normal-appearing white matter." This method assumes that the average CBF value in WM is not significantly dependent on age, gender, and physiologic conditions, and calculates the population-averaged correction factor by setting WM CBF values to 22 ml/100 g/min (11-13). However, Mukherjee et al. (14) have shown that the individual subject-to-subject correction factor is favored over the population-averaged correction fac...

ObjectivesCumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants.Methods224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed.ResultsIncreasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment.ConclusionsGreater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters.

Purpose:To improve the accuracy of dynamic susceptibility contrast (DSC) measurements of cerebral blood flow (CBF) and volume (CBV). Materials and Methods:In eight volunteers, steady-state CBV (CBV SS ) was measured using TrueFISP readout of inversion recovery (IR) before and after injection of a bolus of contrast. A standard DSC (STD) perfusion measurement was performed by echo-planar imaging (EPI) during passage of the bolus and subsequently used to calculate the CBF (CBF DSC ) and CBV (CBV DSC ). The ratio of CBV SS to CBV DSC was used to calibrate measurements of CBV and CBF on a subject-by-subject basis. Results:Agreement of values of CBV (1.77 Ϯ 0.27 mL/100 g in white matter (WM), 3.65 Ϯ 1.04 mL/100 g in gray matter (GM)), and CBF (23.6 Ϯ 2.4 mL/(100 g min) in WM, 57.3 Ϯ 18.2 mL/(100 g min) in GM) with published goldstandard values shows improvement after calibration. An F-test comparison of the coefficients of variation of the CBV and CBF showed a significant reduction, with calibration, of the variability of CBV in WM (P Ͻ 0.001) and GM (P Ͻ 0.03), and of CBF in WM (P Ͻ 0.0001). Conclusion:The addition of a CBV SS measurement to an STD measurement of cerebral perfusion improves the accuracy of CBV and CBF measurements. The method may prove useful for assessing patients suffering from acute stroke.

The steady-state (SS) approach has been proposed to measure quantitative cerebral blood volume (CBV). However, it is known that the CBV value in SS (CBV SS ) is subject to error resulting from the effects of water diffusion from the intra-to extravascular space. CBV SS measurements were simulated in both fastand no-water-exchange limits, and compared with measured CBV SS values to determine which limiting case is appropriate. Twenty-eight patients were scanned with a segmented LookLocker echo-planar imaging (LL-EPI) sequence before and after the injection of 0.1 mmol/kg of a T 1 -shortening contrast agent. Signal changes and T 1 values of brain parenchyma and the blood pool were measured pre-and postcontrast. These signal changes and T 1 values, in combination with the simulated results, were used to estimate water-exchange rates. We found that the intra-to extravascular water-exchange rates in white matter (WM) and gray matter (GM) were 0.9 and 1.6 s -1 , respectively. With these water-exchange rates, the fast-water-ex- In recent years MRI techniques have been developed to quantify a variety of physiologic parameters that reflect pathology. Parameters related to tissue perfusion have been shown to reflect underlying pathophysiology in a variety of diseases of the central nervous system, including ischemic stroke, tumor neovascularity, neoplasia, and Alzheimer's disease (1-5). Imaging techniques to measure relative cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) have been established (6). However, reliable quantification of these parameters has been elusive.When the blood-brain barrier (BBB) is intact, one can measure CBV values using contrast-enhanced MRI by comparing T 1 maps or T 1 -weighted images measured before and after the intravascular injection of a T 1 -shortening contrast agent (7,8). This approach is conventionally referred to as the steady-state CBV (CBV SS ) measurement. However, quantification of CBV SS has been problematic due to under-or overestimation resulting from the continual exchange of water from the intravascular space (9). The effect of water exchange has been extensively modeled (10), and there are predictable trends that depend on the approximations of the exchange rate. There are two limiting cases-the "fast-exchange" and "no-exchange" limits-that require different approaches to calculate CBV SS .We attempted to determine which limiting case of the exchange rate is valid in healthy tissue by performing direct measurements in humans. First we simulated CBV measurement in both fast-and no-water-exchange limits to determine the behavior in the range of values relevant to normal white matter (WM) and gray matter (GM). We then compared these simulated results with data acquired in patients. Then we used in vivo data to determine which limiting case is valid, and to determine the intravascular (to extravascular) and extravascular (to intravascular) water-exchange rates. Finally, with the optimum values for exchange rate determined, we developed a techni...

Repetitive head trauma is a risk factor for Alzheimer's disease and is the primary cause of chronic traumatic encephalopathy. However, little is known about the natural history of, and risk factors for, chronic traumatic encephalopathy or about means of early detection and intervention. The Professional Fighters Brain Health Study is a longitudinal study of active professional fighters (boxers and mixed martial artists), retired professional fighters, and controls matched for age and level of education. The main objective of the Professional Fighters Brain Health Study is to determine the relationships between measures of head trauma exposure and other potential modifiers and changes in brain imaging and neurological and behavioral function over time. The study is designed to extend over 5 years, and we anticipate enrollment of more than 400 boxers and mixed martial artists. Participants will undergo annual evaluations that include 3-tesla magnetic resonance imaging scanning, computerized cognitive assessments, speech analysis, surveys of mood and impulsivity, and blood sampling for genotyping and exploratory biomarker studies. Statistical models will be developed and validated to predict early and progressive changes in brain structure and function. A composite fight exposure index, developed as a summary measure of cumulative traumatic exposure, shows promise as a predictor of brain volumes and cognitive function.

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Purpose:To derive a magnetic resonance (MR)-based imaging metric that refl ects local perfusion changes resulting from the administration of angiogenic-inhibiting chemotherapy in patients with recurrent glioblastoma multiforme (GBM). Materials and Methods:In this retrospective Institutional Review Board-approved HIPAA-compliant study, 16 patients (12 men, four women; mean age, 51.8 years 6 15.1 [standard deviation]) with recurrent GBM received bevacizumab every 3 weeks (15 mg per kilogram of body weight) as part of a clinical trial. Baseline MR images were acquired, and follow-up images were acquired every 6 weeks thereafter until tumor progression or death. Imaging included perfusion and T1-weighted contrast material-enhanced MR imaging. Perfusion images were analyzed both with and without correction for contrast material leakage. The volumes of interest were selected as enhancing voxels on T1-weighted contrast-enhanced MR images. Relative cerebral blood volume (rCBV) maps were created from analysis of MR perfusion images. The volumes of interest were used to calculate the following parameters: size, mean rCBV, mean leakage coeffi cient K 2 , and hyperperfusion volume (HPV), which is the fraction of the tumor with an rCBV higher than a predetermined threshold. Percent change in each parameter from baseline to fi rst follow-up was compared with time to progression (TTP) by using a Cox proportional hazards model with calculation of hazard ratios. Results:The most signifi cant hazard ratio was seen with a D HPV cutoff of rCBV greater than 1.00 (hazard ratio, 1.077; 95% confi dence interval: 1.026, 1.130; P = .002). The only significant ratios greater than one were those that resulted from perfusion calculated as mean rCBV and D HPV. The ratios were also higher after correction for leakage. Conclusion:This pilot study derived an imaging metric (HPV) that refl ects local perfusion changes in GBMs. This metric was found to show a signifi cantly improved correlation to TTP as compared with more commonly used metrics.q RSNA, 2010 1

We present a method of quantifying cerebral blood volume using dynamic susceptibility contrast. Our approach combines T(2)-weighted echo planar imaging (EPI) pulse sequences and reference scans that determine the parenchymal T(1) changes resulting from an injection of a gadolinium chelate. This combined T(2)- and T(1)-weighted approach (the "bookend" technique) has been shown to be effective in the quantification of gradient-echo (GRE) (T(2)*-weighted) perfusion images but has not been applied to spin-echo EPI (SE-EPI) (T(2)-weighted) images. The physics related to blood volume measurement based on T(2)- and T(2)*-weighted EPI sequences is known to be different, and there is a question as to whether the bookend approach is effective with SE-EPI. We have compared the quantitative SE-EPI with GRE-EPI in a series of patients with central nervous system (CNS) tumors. We found that quantitative cerebral blood volume (qCBV) values for SE-EPI and GRE-EPI are in agreement with each other and with historical reference values. A subjective evaluation of image quality showed that image quality in the SE-EPI scans was high and exhibited high interreader agreement. We conclude that measuring qCBV using the bookend technique with SE-EPI images is possible and may be a viable alternative to GRE-EPI in the evaluation of CNS tumors.