Phosphocreatine (PCr) plays a vital role in neuron and myocyte energy homeostasis. Currently, there are no routine diagnostic tests to noninvasively map PCr distribution with clinically relevant ...spatial resolution and scan time. Here, we demonstrate that artificial neural network-based chemical exchange saturation transfer (ANNCEST) can be used to rapidly quantify PCr concentration with robust immunity to commonly seen MRI interferences. High-quality PCr mapping of human skeletal muscle, as well as the information of exchange rate, magnetic field and radio-frequency transmission inhomogeneities, can be obtained within 1.5 min on a 3 T standard MRI scanner using ANNCEST. For further validation, we apply ANNCEST to measure the PCr concentrations in exercised skeletal muscle. The ANNCEST outcomes strongly correlate with those from
P magnetic resonance spectroscopy (R = 0.813, p < 0.001, t test). These results suggest that ANNCEST has potential as a cost-effective and widely available method for measuring PCr and diagnosing related diseases.
Background Current definitions of psychotic illness lack biological validity, motivating alternative biomarker-driven disease entities. Building on experimental constructs—Biotypes—previously ...developed from cognitive and neurophysiologic measures (1), we contrast brain anatomy characteristics across Biotypes alongside conventional diagnoses, examining gray matter density (GMD) as an independent validator for the Biotypes. Methods Whole brain GMD measures were examined in probands, their relatives, and healthy subjects organized by Biotype, and then by DSM diagnosis (n=1,409), using Voxel-Based Morphometry with subsequent subject-level regional characterization and distribution analyses. Results Probands grouped by Biotype vs. healthy showed a step-wise pattern of GMD reductions: Biotype1, extensive and diffusely distributed GMD loss, with the largest effects in frontal, anterior/middle cingulate, temporal regions; Biotype2, intermediate and more localized reductions, with the largest effects in insula, fronto-temporal regions; Biotype3, small reductions localized to anterior limbic regions. Relatives showed regionally distinct GMD reductions vs. healthy, with primarily anterior (fronto-temporal) effects in Biotype1; posterior (temporo-parieto-cerebellar) in Biotype2; and normal GMD in Biotype3. Schizophrenia and schizoaffective probands vs. healthy showed overlapping GMD reductions, with the largest effects in fronto-temporal and parietal regions; psychotic bipolar probands had small reductions, primarily in frontal regions. GMD changes in relatives followed regional patterns observed in probands, albeit less extensive. Biotypes showed stronger between-group separation based on GMD than the conventional diagnoses, and were the strongest predictor of GMD change. Conclusions The GMD biomarkers depicted unique brain structure characteristics within Biotypes consistent with their cognitive and sensorimotor profiles, and provided stronger discrimination for biologically-driven Biotypes than symptom-based diagnoses.
Abstract Arterial-spin-labeling (ASL) magnetic resonance imaging (MRI) provides a noninvasive tool to measure cerebral blood flow (CBF) and is increasingly used as a surrogate for baseline neural ...activity. However, the power of ASL MRI in detecting CBF differences between patient and control subjects is hampered by inter-subject variations in global CBF, which are associated with non-neural factors and may contribute to the noise in the across-group comparison. Here, we investigated the sensitivity of this technique and proposed a normalization strategy to better detect such a difference. A “model” situation was employed in which two visual stimuli (i.e. cross fixation and flashing checkerboard) were presented to two groups of subjects to mimic “control” and “patient” groups (N=7 for each group), respectively. It was found that absolute CBF (aCBF) in the occipital lobe in the checkerboard group was 26.0% greater compared to the fixation group, but the level of significance was modest ( P =.03). In contrast, when normalizing the CBF with whole-brain CBF or CBF in a reference region termed relative CBF (rCBF), the statistical significance was improved considerably ( P <.003). For voxel-based analysis, the rCBF indices correctly detected CBF differences in the occipital lobe in the across-group comparison, while aCBF failed to detect any significant cluster using the same statistical threshold. We also performed Monte Carlo simulation to confirm the experimental findings and found that the power improvement was most pronounced when signal-to-noise-ratio is moderate and the underlying CBF difference was small. The simulation also showed that, with the proposed normalization, a detection power of 80% can be achieved using a sample size of about 20. In summary, rCBF is a more sensitive index to detect small differences in CBF, rather than the much-sought-after aCBF, since it reduces data noise caused by inter-subject variations in global CBF.
Objective
Blood–brain barrier (BBB) breakdown has been suggested to be an early biomarker in human cognitive impairment. However, the relationship between BBB breakdown and brain pathology, most ...commonly Alzheimer disease (AD) and vascular disease, is still poorly understood. The present study measured human BBB function in mild cognitive impairment (MCI) patients on 2 molecular scales, specifically BBB's permeability to water and albumin molecules.
Methods
Fifty‐five elderly participants were enrolled, including 33 MCI patients and 22 controls. BBB permeability to water was measured with a new magnetic resonance imaging technique, water extraction with phase contrast arterial spin tagging. BBB permeability to albumin was determined using cerebrospinal fluid (CSF)/serum albumin ratio. Cognitive performance was assessed by domain‐specific composite scores. AD pathology (including CSF Aβ and ptau) and vascular risk factors were examined.
Results
Compared to cognitively normal subjects, BBB in MCI patients manifested an increased permeability to small molecules such as water but was no more permeable to large molecules such as albumin. BBB permeability to water was found to be related to AD markers of CSF Aβ and ptau. On the other hand, BBB permeability to albumin was found to be related to vascular risk factors, especially hypercholesterolemia, but was not related to AD pathology. BBB permeability to small molecules, but not to large molecules, was found to be predictive of cognitive function.
Interpretation
These findings provide early evidence that BBB breakdown is related to both AD and vascular risks, but their effects can be differentiated by spatial scales. BBB permeability to small molecules has a greater impact on cognitive performance. ANN NEUROL 2021;90:227–238
Characterizing the effect of oxygen (O2) modulation on the brain may provide a better understanding of several clinically relevant problems, including acute mountain sickness and hyperoxic therapy in ...patients with traumatic brain injury or ischemia. Quantifying the O2 effects on brain metabolism is also critical when using this physiologic maneuver to calibrate functional magnetic resonance imaging (fMRI) signals. Although intuitively crucial, the question of whether the brain's metabolic rate depends on the amount of O2 available has not been addressed in detail previously. This can be largely attributed to the scarcity and complexity of measurement techniques. Recently, we have developed an MR method that provides a noninvasive (devoid of exogenous agents), rapid (<5 minutes), and reliable (coefficient of variant, CoV <3%) measurement of the global cerebral metabolic rate of O2 (CMRO2). In the present study, we evaluated metabolic and vascular responses to manipulation of the fraction of inspired O2 (FiO2). Hypoxia with 14% FiO2 was found to increase both CMRO2 (5.0±2.0%, N=16, P=0.02) and cerebral blood flow (CBF) (9.8±2.3%, P<0.001). However, hyperoxia decreased CMRO2 by 10.3±1.5% (P<0.001) and 16.9±2.7% (P<0.001) for FiO2 of 50% and 98%, respectively. The CBF showed minimal changes with hyperoxia. Our results suggest that modulation of inspired O2 alters brain metabolism in a dose-dependent manner.
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