Using the adiabatic approximation, which assumes that the tracer concentration in parenchymal tissue changes slowly relative to that in capillaries, we derived a time-domain, closed-form solution of the tissue homogeneity model. This solution, which is called the adiabatic solution, is similar in form to those of two-compartment models. Owing to its simplicity, the adiabatic solution can be used in CBF experiments in which kinetic data with only limited time resolution or signal-to-noise ratio, or both, are obtained. Using computer simulations, we investigated the accuracy and the precision of the parameters in the adiabatic solution for values that reflect 2H-labeled water (D2O) clearance from the brain (see Part II). It was determined that of the three model parameters, (1) the vascular volume (Vi), (2) the product of extraction fraction and blood flow (EF), and (3) the clearance rate constant (kadb), only the last one could be determined accurately, and therefore CBF must be determined from this parameter only. From the error analysis of the adiabatic solution, it was concluded that for the D2O clearance experiments described in Part II, the coefficient of variation of CBF was approximately 7% in gray matter and 22% in white matter.

All of the proposed novel methods have an average global performance within likely acceptable limits (±5% of CT-based reference), and the main difference among the methods was found in the robustness, outlier analysis, and clinical feasibility. Overall, the best performing methods were MR-ACBOSTON, MR-ACMAXPROB, MR-ACRESOLUTE and MR-ACUCL, ordered alphabetically. These methods all minimized the number of outliers, standard deviation, and average global and local error. The methods MR-ACMUNICH and MR-ACCAR-RiDR were both within acceptable quantitative limits, so these methods should be considered if processing time is a factor. The method MR-ACSEGBONE also demonstrates promising results, and performs well within the likely acceptable quantitative limits. For clinical routine scans where processing time can be a key factor, this vendor-provided solution currently outperforms most methods. With the performance of the methods presented here, it may be concluded that the challenge of improving the accuracy of MR-AC in adult brains with normal anatomy has been solved to a quantitatively acceptable degree, which is smaller than the quantification reproducibility in PET imaging.

A primary focus of neurointensive care is the prevention of secondary brain injury, mainly caused by ischemia. A noninvasive bedside technique for continuous monitoring of cerebral blood flow (CBF) could improve patient management by detecting ischemia before brain injury occurs. A promising technique for this purpose is diffuse correlation spectroscopy (DCS) since it can continuously monitor relative perfusion changes in deep tissue. In this study, DCS was combined with a time-resolved near-infrared technique (TR-NIR) that can directly measure CBF using indocyanine green as a flow tracer. With this combination, the TR-NIR technique can be used to convert DCS data into absolute CBF measurements. The agreement between the two techniques was assessed by concurrent measurements of CBF changes in piglets. A strong correlation between CBF changes measured by TR-NIR and changes in the scaled diffusion coefficient measured by DCS was observed (R2 = 0.93) with a slope of 1.05 ± 0.06 and an intercept of 6.4 ± 4.3% (mean ± standard error).

Quantification of water permeability can improve the accuracy of perfusion measurements obtained with arterial spin labeling (ASL) methods, and may provide clinically relevant information regarding the functional status of the microvasculature. The amount of labeled water in the vascular and tissue compartments in an ASL experiment can be estimated based on their distinct diffusion characteristics, and in turn, water permeability determined from the relative vascular and tissue contributions. In the present study, a hybrid magnetic resonance imaging technique was introduced by marrying a continuous ASL method with a twice-refocused spin-echo diffusion sequence. Series of diffusion-weighted ASL signals were acquired with systematically varied b values. The signals were modeled with fast and slow decaying components that were associated with the vascular and tissue compartments, respectively. The relative amount of labeled water in the tissue compartment increased from 61% to 74% and to 86% when the postlabeling delay time was increased from 0.8 to 1.2 and to 1.5 secs. With a b value of 50 secs/mm 2 , the capillary contribution (fast component) of the ASL signal could be effectively minimized. Using the single-pass approximation model, the water permeability of gray matter in the human brain was estimated based on the derived relative water fractions in the tissue and microvasculature. The potential for in vivo magnetic resonance mapping of water permeability was showed using two diffusion weighted ASL measurements with b = 0 and 50 secs/mm 2 in both healthy subjects and a case of brain tumor.