Near-Term Fetal Hypoxia-Ischemia in Rabbits MRI Can Predict Muscle Tone Abnormalities and Deep Brain Injury

Background and Purpose-The pattern of antenatal brain injury varies with gestational age at the time of insult. Deep brain nuclei are often injured at older gestational ages. Having previously shown postnatal hypertonia after preterm fetal rabbit hypoxia-ischemia, the objective of this study was to investigate the causal relationship between the dynamic regional pattern of brain injury on MRI and the evolution of muscle tone in the near-term rabbit fetus. Methods-Serial MRI was performed on New Zealand white rabbit fetuses to determine equipotency of fetal hypoxia-ischemia during uterine ischemia comparing 29 days gestation (E29, 92% gestation) with E22 and E25. E29 postnatal kits at 4, 24, and 72 hours after hypoxia-ischemia underwent T2- and diffusion-weighted imaging. Quantitative assessments of tone were made serially using a torque apparatus in addition to clinical assessments. Results-Based on the brain apparent diffusion coefficient, 32 minutes of uterine ischemia was selected for E29 fetuses. At E30, 58% of the survivors manifested hind limb hypotonia. By E32, 71% of the hypotonic kits developed dystonic hypertonia. Marked and persistent apparent diffusion coefficient reduction in the basal ganglia, thalamus, and brain stem was predictive of these motor deficits. Conclusions-MRI observation of deep brain injury 6 to 24 hours after near-term hypoxia-ischemia predicts dystonic hypertonia postnatally. Torque-displacement measurements indicate that motor deficits in rabbits progressed from initial hypotonia to hypertonia, similar to human cerebral palsy, but in a compressed timeframe. The presence of deep brain injury and quantitative shift from hypo-to hypertonia may identify patients at risk for developing cerebral palsy. (Stroke. 2012;43:2757-2763.)

Mapping hippocampal and ventricular change in Alzheimer disease

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Fifty-two high-resolution MRI scans were acquired from 12 AD patients (age: 68.4 ± 1.9 years) and 14 matched controls (age: 71.4 ± 0.9 years), each scanned twice (2.1 ± 0.4 years apart). 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials.

Mapping hippocampal and ventricular change in Alzheimer disease

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Fifty-two high-resolution MRI scans were acquired from 12 AD patients (age: 68.4 +/- 1.9 years) and 14 matched controls (age: 71.4 +/- 0.9 years), each scanned twice (2.1 +/- 0.4 years apart). 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials. (C) 2004 Elsevier Inc. All rights reserved.

Relación entre atrofia cortical difusa y desempeño cognitivo : estudio en población mayor de 60 años en un hospital universitario en la ciudad de Bogotá

El presente trabajo tuvo como objetivo evaluar la existencia de la relación entre la atrofia cortical difusa objetivada por neuroimagenes cerebrales y desempeños cognitivos determinados mediante la aplicación de pruebas neuropsicológicas que evalúan memoria de trabajo, razonamiento simbólico verbal y memoria anterógrada declarativa. Participaron 114 sujetos reclutados en el Hospital Universitario Mayor Méderi de la ciudad de Bogotá mediante muestreo de conveniencia. Los resultados arrojaron diferencias significativas entre los dos grupos (pacientes con diagnóstico de atrofia cortical difusa y pacientes con neuroimagenes interpretadas como dentro de los límites normales) en todas las pruebas neuropsicológicas aplicadas. Respecto a las variables demográficas se pudo observar que el grado de escolaridad contribuye como factor neuroprotector de un posible deterioro cognitivo. Tales hallazgos son importantes para determinar protocoles tempranos de detección de posible instalación de enfermedades neurodegenerativas primarias.

Effects of MRI scan acceleration on brain volume measurement consistency.

PURPOSE: To evaluate the effects of recent advances in magnetic resonance imaging (MRI) radiofrequency (RF) coil and parallel imaging technology on brain volume measurement consistency. MATERIALS AND METHODS: In all, 103 whole-brain MRI volumes were acquired at a clinical 3T MRI, equipped with a 12- and 32-channel head coil, using the T1-weighted protocol as employed in the Alzheimer's Disease Neuroimaging Initiative study with parallel imaging accelerations ranging from 1 to 5. An experienced reader performed qualitative ratings of the images. For quantitative analysis, differences in composite width (CW, a measure of image similarity) and boundary shift integral (BSI, a measure of whole-brain atrophy) were calculated. RESULTS: Intra- and intersession comparisons of CW and BSI measures from scans with equal acceleration demonstrated excellent scan-rescan accuracy, even at the highest acceleration applied. Pairs-of-scans acquired with different accelerations exhibited poor scan-rescan consistency only when differences in the acceleration factor were maximized. A change in the coil hardware between compared scans was found to bias the BSI measure. CONCLUSION: The most important findings are that the accelerated acquisitions appear to be compatible with the assessment of high-quality quantitative information and that for highest scan-rescan accuracy in serial scans the acquisition protocol should be kept as consistent as possible over time. J. Magn. Reson. Imaging 2012;36:1234-1240. ©2012 Wiley Periodicals, Inc.

Quantitative MRI of spinal cord injury in a rat model: Correlative studies

Serial quantitative and correlative studies of experimental spinal cord injury (SCI) in rats were conducted using three-dimensional magnetic resonance imaging (MRI). Correlative measures included morphological histopathology, neurobehavioral measures of functional deficit, and biochemical assays for N-acetyl-aspartate (NAA), lactate, pyruvate, and ATP. A spinal cord injury device was characterized and provided a reproducible injury severity. Injuries were moderate and consistent to within $\pm$20% (standard deviation). For MRI, a three-dimensional implementation of the single spin-echo FATE (Fast optimum angle, short TE) pulse sequence was used for rapid acquisition, with a 128 x 128 x 32 (x,y,z) matrix size and a 0.21 x 0.21 x 1.5 mm resolution. These serial studies revealed a bimodal characteristic in the evolution in MRI pathology with time. Early and late phases of SCI pathology were clearly visualized in $T\sb2$-weighted MRI, and these corresponded to specific histopathological changes in the spinal cord. Centralized hypointense MRI regions correlated with evidence of hemorrhagic and necrotic tissue, while surrounding hyperintense regions represented edema or myelomalacia. Unexpectedly, $T\sb2$-weighted MRI pathology contrast at 24 hours after injury appeared to subside before peaking at 72 hours after injury. This change is likely attributable to ongoing secondary injury processes, which may alter local $T\sb2$ values or reduce the natural anisotropy of the spinal cord. MRI, functional, and histological measures all indicated that 72 hours after injury was the temporal maximum for quantitative measures of spinal cord pathology. Thereafter, significant improvement was seen only in neurobehavioral scores. Significant correlations were found between quantitated MRI pathology and histopathology. Also, NAA and lactate levels correlated with behavioral measures of the level of function deficit. Asymmetric (rostral/caudal) changes in NAA and lactate due to injury indicate that rostral and caudal segments from the injury site are affected differently by the injury. These studies indicate that volumetric quantitation of MRI pathology from $T\sb2$-weighted images may play an important role in early prediction of neurologic deficit and spinal cord pathology. The loss of $T\sb2$ contrast at 24 hours suggests MR may be able to detect certain delayed mechanisms of secondary injury which are not resolved by histopathology or other radiological modalities. Furthermore, in vivo proton magnetic resonance spectroscopy (MRS) studies of SCI may provide a valuable addition source of information about changes in regional spinal cord lactate and NAA levels, which are indicative of local metabolic and pathological changes. ^

Serial [18F]-fluoromisonidazole PET during radiochemotherapy for locally advanced head and neck cancer and its correlation with outcome.

PURPOSE The aim was to assess changes of tumour hypoxia during primary radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their relationship with treatment outcome. MATERIAL AND METHODS Hypoxia was assessed by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV) was defined as TV that showed FMISO uptake ⩾1.4 times blood pool activity. RESULTS Sixteen consecutive patients (T3-4, N+, M0) were included (mean follow-up 31, median 44months). Mean TBRmax decreased significantly (p<0.05) from 1.94 to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2=5.8ml, HSV3=0.3ml) were significantly (p<0.05) smaller than at baseline (HSV1=15.8ml). Kaplan-Meier plots of local recurrence free survival stratified at the median TBRmax showed superior local control for less hypoxic tumours, the difference being significant at baseline and after 2weeks (p=0.031, p=0.016). CONCLUSIONS FMISO-PET documented that in most HNC reoxygenation starts early during RCT and is correlated with better outcome.

Comparison of linear and non-linear 2D+T registration methods for DE-MRI cardiac perfusion studies

A series of motion compensation algorithms is run on the challenge data including methods that optimize only a linear transformation, or a non-linear transformation, or both – first a linear and then a non-linear transformation. Methods that optimize a linear transformation run an initial segmentation of the area of interest around the left myocardium by means of an independent component analysis (ICA) (ICA-*). Methods that optimize non-linear transformations may run directly on the full images, or after linear registration. Non-linear motion compensation approaches applied include one method that only registers pairs of images in temporal succession (SERIAL), one method that registers all image to one common reference (AllToOne), one method that was designed to exploit quasi-periodicity in free breathing acquired image data and was adapted to also be usable to image data acquired with initial breath-hold (QUASI-P), a method that uses ICA to identify the motion and eliminate it (ICA-SP), and a method that relies on the estimation of a pseudo ground truth (PG) to guide the motion compensation.

Contributions of cell kill and posttreatment tumor growth rates to the repopulation of intracerebral 9L tumors after chemotherapy: An MRI study

The drought of progress in clinical brain tumor therapy provides an impetus for developing new treatments as well as methods for testing therapeutics in animal models. The inability of traditional assays to simultaneously measure tumor size, location, growth kinetics, and cell kill achieved by a treatment complicates the interpretation of therapy experiments in animal models. To address these issues, tumor volume measurements obtained from serial magnetic resonance images were used to noninvasively estimate cell kill values in individual rats with intracerebral 9L tumors after treatment with 0.5, 1, or 2 × LD10 doses of 1,3-bis(2-chloroethyl)-1-nitrosourea. The calculated cell kill values were consistently lower than those reported using traditional assays. A dose-dependent increase in 9L tumor doubling time after treatment was observed that significantly contributed to the time required for surviving cells to repopulate the tumor mass. This study reveals that increases in animal survival are not exclusively attributable to the fraction of tumor cells killed but rather are a function of the cell kill and repopulation kinetics, both of which vary with treatment dose.