Continuous Blood Pressure Monitoring Algorithm using Laser Doppler Flowmetry.

A novel machine learning algorithm is introduced to estimate continuous blood pressure monitoring using Laser Doppler Flowmetry (LDF). LDF provides instantaneous, continuous, and noninvasive measurements of blood flow in a small tissue sample. The proposed algorithm segments the continuous blood flow profile based on heartbeat cycles to subsequently extract multiple features. The beat-to-beat blood pressure was estimated from a multi-layer neural network algorithm using the extracted features. The algorithm was also validated with clinically proven cuff based continuous blood pressure sensors. Mean average error values of 4.54 \sim5.37 mmHg were observed, which conform to a Grade B/C category per the IEEE standard 1708-2014 for cuffless blood pressure measuring devices.

Towards development of a mobile RF Doppler sensor for continuous heart rate variability and blood pressure monitoring.

The standard in noninvasive blood pressure (BP) measurement is an inflatable cuff device based on the oscillometric method, which poses several practical challenges for continuous BP monitoring. Here, we present a novel ultra-wide band RF Doppler radar sensor for next-generation mobile interface for the purpose of characterizing fluid flow speeds, and for ultimately measuring cuffless blood flow in the human wrist. The system takes advantage of the 7.1~10.5 GHz ultra-wide band signals which can reduce transceiver complexity and power consumption overhead. Moreover, results obtained from hardware development, antenna design and human wrist modeling, and subsequent phantom development are reported. Our comprehensive lab bench system setup with a peristaltic pump was capable of characterizing various speed flow components during a linear velocity sweep of 5~62 cm/s. The sensor holds potential for providing estimates of heart rate and blood pressure.

Smartphone-Based Bioelectrical Impedance Analysis Devices for Daily Obesity Management.

Current bioelectric impedance analysis (BIA) systems are often large, cumbersome devices which require strict electrode placement on the user, thus inhibiting mobile capabilities. In this work, we developed a handheld BIA device that measures impedance from multiple frequencies (5 kHz~200 kHz) with four contact electrodes and evaluated the BIA device against standard body composition analysis systems: a dual-energy X-ray absorptiometry (DXA) system (GE Lunar Prodigy, GE Healthcare, Buckinghamshire, UK) and a whole-body BIA system (InBody S10, InBody, Co. Ltd, Seoul, Korea). In the study, 568 healthy participants, varying widely in body mass index, age, and gender, were recruited at two research centers: the Samsung Medical Center (SMC) in South Korea and the Pennington Biomedical Research Center (PBRC) in the United States. From the measured impedance data, we analyzed individual body fat and skeletal muscle mass by applying linear regression analysis against target reference data. Results indicated strong correlations of impedance measurements between the prototype pathways and corresponding InBody S10 electrical pathways (R = 0.93, p < 0.0001). Additionally, body fat estimates from DXA did not yield significant differences (p > 0.728 (paired t-test), DXA mean body fat 29.45 ± 10.77 kg, estimated body fat 29.52 ± 12.53 kg). Thus, this portable BIA system shows a promising ability to estimate an individual's body composition that is comparable to large stationary BIA systems.

Mobile evaluation of human energy balance and weight control: Potential for future developments.

Quantification of energy storage is essential in understanding energy balance and can be determined by bioelectrical impedance analysis (BIA). Here, we have developed a smartphone form factor multi-frequency BIA device that incorporates an analog front end for body composition measurements. The device was compared against a reference gel-electrode based BIA system in a clinical trial of 311 subjects for predicting BIA equations by calibrating the impedance index to body composition data from dual energy X-ray absorptiometry (DXA). Strong correlations were observed between DXA-based lean soft tissue and the impedance index generated at 50 KHz (R(2)=0.87; p<;0.001). A similar trend was also evident at higher frequencies which matched results from the reference gel-electrode BIA device. The findings support the role of our consumer-oriented mobile Health initiative for multi-frequency BIA assessments to aid weight management.

Bone mineral (31)P and matrix-bound water densities measured by solid-state (31)P and (1)H MRI.

Bone is a composite material consisting of mineral and hydrated collagen fractions. MRI of bone is challenging because of extremely short transverse relaxation times, but solid-state imaging sequences exist that can acquire the short-lived signal from bone tissue. Previous work to quantify bone density via MRI used powerful experimental scanners. This work seeks to establish the feasibility of MRI-based measurement on clinical scanners of bone mineral and collagen-bound water densities, the latter as a surrogate of matrix density, and to examine the associations of these parameters with porosity and donors' age. Mineral and matrix-bound water images of reference phantoms and cortical bone from 16 human donors, aged 27-97 years, were acquired by zero-echo-time 31-phosphorus ((31)P) and 1-hydrogen ((1)H) MRI on whole body 7T and 3T scanners, respectively. Images were corrected for relaxation and RF inhomogeneity to obtain density maps. Cortical porosity was measured by micro-computed tomography (µCT), and apparent mineral density by peripheral quantitative CT (pQCT). MRI-derived densities were compared to X-ray-based measurements by least-squares regression. Mean bone mineral (31)P density was 6.74 ± 1.22 mol/l (corresponding to 1129 ± 204 mg/cc mineral), and mean bound water (1)H density was 31.3 ± 4.2 mol/l (corresponding to 28.3 ± 3.7 %v/v). Both (31)P and bound water (BW) densities were correlated negatively with porosity ((31)P: R(2) = 0.32, p < 0.005; BW: R(2) = 0.63, p < 0.0005) and age ((31)P: R(2) = 0.39, p < 0.05; BW: R(2) = 0.70, p < 0.0001), and positively with pQCT density ((31)P: R(2) = 0.46, p < 0.05; BW: R(2) = 0.50, p < 0.005). In contrast, the bone mineralization ratio (expressed here as the ratio of (31)P density to bound water density), which is proportional to true bone mineralization, was found to be uncorrelated with porosity, age or pQCT density. This work establishes the feasibility of image-based quantification of bone mineral and bound water densities using clinical hardware.

Cortical bone water concentration: dependence of MR imaging measures on age and pore volume fraction.

PURPOSE: To quantify bulk bone water to test the hypothesis that bone water concentration (BWC) is negatively correlated with bone mineral density (BMD) and is positively correlated with age, and to propose the suppression ratio (SR) (the ratio of signal amplitude without to that with long-T2 suppression) as a potentially stronger surrogate measure of porosity, which is evaluated ex vivo and in vivo. MATERIALS AND METHODS: Human subject studies were conducted in compliance with institutional review board and HIPAA regulations. Healthy men and women (n = 72; age range, 20-80 years) were examined with a hybrid radial ultrashort echo time magnetic resonance (MR) imaging sequence at 3.0 T, and BWC was determined in the tibial midshaft. In a subset of 40 female subjects, the SR was measured with a similar sequence. Cortical volumetric BMD (vBMD) was measured by means of peripheral quantitative computed tomography (CT). The method was validated against micro-CT-derived porosity in 13 donor human cortical bone specimens. Associations among parameters were evaluated by using standard statistical tools. RESULTS: BWC was positively correlated with age (r = 0.52; 95% confidence interval [CI]: 0.22, 0.73; P = .002) and negatively correlated with vBMD at the same location (r = -0.57; 95% CI: -0.76, -0.29; P < .001). Data were suggestive of stronger associations with SR (r = 0.64, 95% CI: 0.39, 0.81, P < .001 for age; r = -0.67, 95% CI: -0.82, -0.43, P < .001 for vBMD; P < .001 for both), indicating that SR may be a more direct measure of porosity. This interpretation was supported by ex vivo measurements showing SR to be strongly positively correlated with micro-CT porosity (r = 0.88; 95% CI: 0.64, 0.96; P < .001) and with age (r = 0.87; 95% CI: 0.62, 0.96; P < .001). CONCLUSION: The MR imaging-derived SR may serve as a biomarker for cortical bone porosity that is potentially superior to BWC, but corroboration in larger cohorts is indicated.

Effects of testosterone and growth hormone on the structural and mechanical properties of bone by micro-MRI in the distal tibia of men with hypopituitarism.

CONTEXT: Severe deficiencies of testosterone (T) and GH are associated with low bone mineral density (BMD) and increased fracture risk. Replacement of T in hypogonadal men improves several bone parameters. Replacement of GH in GH-deficient men improves BMD. OBJECTIVE: Our objective was to determine whether T and GH treatment together improves the structural and mechanical parameters of bone more than T alone in men with hypopituitarism. DESIGN AND SUBJECTS: This randomized, prospective, 2-year study included 32 men with severe deficiencies of T and GH due to panhypopituitarism. INTERVENTION: Subjects were randomized to receive T alone (n = 15) or T and GH (n = 17) for 2 years. MAIN OUTCOME MEASURES: We evaluated magnetic resonance microimaging-derived structural (bone volume fraction [BVF] and trabecular thickness) and mechanical (axial stiffness [AS], a measure of bone strength) properties of the distal tibia at baseline and after 1 and 2 years of treatment. RESULTS: Treatment with T and GH did not affect BVF, thickness, or AS differently from T alone. T treatment in all subjects for 2 years increased trabecular BVF by 9.6% (P < .0001), trabecular thickness by 2.6% (P < .001), and trabecular AS by 9.8% (P < .001). In contrast, testosterone treatment in all subjects significantly increased cortical thickness by 2.4% (P < .01) but decreased cortical BVF by -4.7% (P < .01) and cortical AS by -6.9% (P < .01). CONCLUSION: Combined T and GH treatment of men with hypopituitarism for 2 years did not improve the measured structural or mechanical parameters of the distal tibia more than T alone. However, testosterone significantly increased the structural and mechanical properties of trabecular bone but decreased most of these properties of cortical bone, illustrating the potential importance of assessing trabecular and cortical bone separately in future studies of the effect of testosterone on bone.

Potential of in vivo MRI-based nonlinear finite-element analysis for the assessment of trabecular bone post-yield properties.

PURPOSE: Bone strength is the key factor impacting fracture risk. Assessment of bone strength from high-resolution (HR) images have largely relied on linear micro-finite element analysis (µFEA) even though failure always occurs beyond the yield point, which is outside the linear regime. Nonlinear µFEA may therefore be more informative in predicting failure behavior. However, existing nonlinear models applied to trabecular bone (TB) have largely been confined to micro-computed tomography (µCT) and, more recently, HR peripheral quantitative computed tomography (HR-pQCT) images, and typically have ignored evaluation of the post-yield behavior. The primary purpose of this work was threefold: (1) to provide an improved algorithm and program to assess TB yield as well as post-yield properties; (2) to explore the potential benefits of nonlinear µFEA beyond its linear counterpart; and (3) to assess the feasibility and practicality of performing nonlinear analysis on desktop computers on the basis of micro-magnetic resonance (µMR) images obtained in vivo in patients. METHODS: A method for nonlinear µFE modeling of TB yield as well as post-yield behavior has been designed where material nonlinearity is captured by adjusting the tissue modulus iteratively according to the tissue-level effective strain obtained from linear analysis using a computationally optimized algorithm. The software allows for images at in vivo µMRI resolution as input with retention of grayscale information. Associations between axial stiffness estimated from linear analysis and yield as well as post-yield parameters from nonlinear analysis were investigated from in vivo µMR images of the distal tibia (N = 20; ages: 58-84) and radius (N = 20; ages: 50-75). RESULTS: All simulations were completed in 1 h or less for 61 strain levels using a desktop computer (dual quad-core Xeon 3.16 GHz CPUs equipped with 40 GB of RAM). Although yield stress and ultimate stress correlated strongly (R(2) > 0.95, p < 0.001) with axial stiffness, toughness correlated moderately at the distal tibia (R(2) = 0.81, p < 0.001) and only weakly at the distal radius (R(2) = 0.34, p = 0.007). Further, toughness was found to vary by up to 16% for bone of very similar axial stiffness (<2%). CONCLUSIONS: The work demonstrates the practicality of nonlinear µFE simulations at in vivo µMRI resolution, as well as its potential for providing additional information beyond that obtainable from linear analysis. The data suggest that a direct assessment of toughness may provide information not captured by stiffness.

Micro-MR imaging-based computational biomechanics demonstrates reduction in cortical and trabecular bone strength after renal transplantation.

PURPOSE: To examine the ability of three-dimensional micro-magnetic resonance (MR) imaging-based computational biomechanics to detect mechanical alterations in trabecular bone and cortical bone in the distal tibia of incident renal transplant recipients 6 months after renal transplantation and compare them with bone mineral density (BMD) outcomes. MATERIALS AND METHODS: The study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained from all subjects. Micro-MR imaging of distal tibial metaphysis was performed within 2 weeks after renal transplantation (baseline) and 6 months later in 49 participants (24 female; median age, 44 years; range, 19-61 years) with a clinical 1.5-T whole-body imager using a modified three-dimensional fast large-angle spin-echo pulse sequence. Micro-finite-element models for cortical bone, trabecular bone, and whole-bone section were generated from each image by delineating the endosteal and periosteal boundaries. Mechanical parameters (stiffness and failure load) were estimated with simulated uniaxial compression tests on the micro-finite-element models. Structural parameters (trabecular bone volume fraction [BV/TV, bone volume to total volume ratio], trabecular thickness [TbTh], and cortical thickness [CtTh]) were computed from micro-MR images. Total hip and spine areal BMD were determined with dual-energy x-ray absorptiometry (DXA). Parameters obtained at the follow-up were compared with the baseline values by using parametric or nonparametric tests depending on the normality of data. RESULTS: All mechanical parameters were significantly lower at 6 months compared with baseline. Decreases in cortical bone, trabecular bone, and whole-bone stiffness were 3.7% (P = .03), 4.9% (P = .03), and 4.3% (P = .003), respectively. Decreases in cortical bone, trabecular bone, and whole-bone failure strength were 7.6% (P = .0003), 6.0% (P = .004), and 5.6% (P = .0004), respectively. Conventional structural measures, BV/TV, TbTh, and CtTh, did not change significantly. Spine BMD decreased by 2.9% (P < .0001), while hip BMD did not change significantly at DXA. CONCLUSION: MR imaging-based micro-finite-element analysis suggests that stiffness and failure strength of the distal tibia decrease over a 6-month interval after renal transplantation.

Predicting trabecular bone elastic properties from measures of bone volume fraction and fabric on the basis of micromagnetic resonance images.

The relationship between fabric (a measure of structural anisotropy) and elastic properties of trabecular bone was examined by invoking morphology and homogenization theory on the basis of micromagnetic resonance images from the distal tibia in specimens (N = 30) and human subjects (N = 16) acquired at a 160 × 160 × 160 µm(3) voxel size. The fabric tensor was mapped in 7.5 × 7.5 × 7.5 mm(3) cubic subvolumes by a three-dimensional mean-intercept-length method. Elastic constants (three Young's and three shear moduli) were derived from linear microfinite element simulations of three-dimensional grayscale bone volume fraction-mapped images. In the specimen data, moduli fit power laws of bone volume fraction (bone volume/total volume) for all three test directions and subvolumes (R(2) = 0.92-0.98) with exponents ranging from 1.3 to 1.8. Weaker linear relationships were found for the in vivo data because of a narrower range in bone volume/total volume. When pooling the data for all test directions and subvolumes, bone volume/total volume predicted elastic moduli less well in the specimens (mean R(2) = 0.74) and not at all in vivo. A model of bone volume/total volume and fabric was highly predictive of microfinite element-derived Young's moduli: mean R(2) s of 0.98 and 0.82 (in vivo). The results show that fabric, an important predictor of bone mechanical properties, can be assessed in the limited resolution and signal-to-noise ratio regime of micromagnetic resonance images.

On the significance of motion degradation in high-resolution 3D µMRI of trabecular bone.

RATIONALE AND OBJECTIVES: Subtle subject movement during high-resolution three-dimensional micro-magnetic resonance imaging of trabecular bone (TB) causes blurring, thereby rendering the data unreliable for quantitative analysis. In this work, the effects of translational and rotational motion displacements were evaluated qualitatively and quantitatively. MATERIALS AND METHODS: In experiment 1, motion was induced by applying various simulated and previously observed in vivo trajectories as phase shifts to k-space or rotation angles to k-space segments of a virtually motion-free data set. In experiment 2, images that were visually free of motion artifacts from two groups of 10 healthy individuals, differing in age, were selected to probe the effects of motion on TB parameters. In both experiments, images were rated for motion severity, and the scores were compared to a focus criterion, the normalized gradient squared. RESULTS: Strong correlations were observed between the motion quality scores and the corresponding normalized gradient squared values (R(2) = 0.52-0.64, P < .01). The results from experiment 1 demonstrated consistently lower image quality and alterations in structural parameters of 9% to 45% with increased amplitude of displacements. In experiment 2, the significant differences in structural parameter group means of the motion-free images were lost upon motion degradation. Autofocusing, a postprocessing correction method, partially recovered the sharpness of the original motion-free images in 13 of 20 subjects. CONCLUSIONS: Quantitative TB structural measures are highly sensitive to subtle motion-induced degradation, which adversely affects precision and statistical power. The results underscore the influence of subject movement in high-resolution three-dimensional micro-magnetic resonance imaging and its correction for TB structure analysis.

Helmholtz-pair transmit coil with integrated receive array for high-resolution MRI of trabecular bone in the distal tibia at 7T.

A Helmholtz-pair local transmit RF coil with an integrated four-element receive array RF coil and foot immobilization platform was designed and constructed for imaging the distal tibia in a whole-body 7T MRI scanner. Simulations and measurements of the B(1) field distribution of the transmit coil are described, along with SAR considerations for operation at 7T. Results of imaging the trabecular bone of three volunteers at 1.5T, 3T and 7T are presented, using identical 1.5T and 3T versions of the 7T four-element receive array. The spatially registered images reveal improved visibility for individual trabeculae and show average gains in SNR of 2.8× and 4.9× for imaging at 7T compared to 3T and 1.5T, respectively. The results thus display an approximately linear dependence of SNR with field strength and enable the practical utility of 7T scanners for micro-MRI of trabecular bone.

Performance of µMRI-Based virtual bone biopsy for structural and mechanical analysis at the distal tibia at 7T field strength.

PURPOSE: To assess the performance of a 3D fast spin echo (FSE) pulse sequence utilizing out-of-slab cancellation through phase alternation and micro-magnetic resonance imaging (µMRI)-based virtual bone biopsy processing methods to probe the serial reproducibility and sensitivity of structural and mechanical parameters of the distal tibia at 7.0T. MATERIALS AND METHODS: The distal tibia of five healthy subjects was imaged at three timepoints with a 3D FSE sequence at 137 × 137 × 410 µm(3) voxel size. Follow-up images were retrospectively 3D registered to baseline images. Coefficients of variation (CV) and intraclass correlation coefficients (ICCs) for measures of scale and topology of the whole tibial trabecular bone (TB) cross-section as well as finite-element-derived Young's and shear moduli of central cuboidal TB subvolumes (8 × 8 × 5 mm(3) ) were evaluated as measures of reproducibility and reliability. Four additional cubic TB subregions (anterior, medial, lateral, and posterior) of similar dimensions were extracted and analyzed to determine associations between whole cross-section and subregional structural parameters. RESULTS: The mean signal-to-noise ratio (SNR) over the 15 image acquisitions was 27.5 ± 2.1. Retrospective registration yielded an average common analysis volume of 67% across the three exams per subject. Reproducibility (mean CV = 3.6%; range, 1.5%-5%) and reliability (ICCs, 0.95-0.99) of all parameters permitted parameter-based discrimination of the five subjects in spite of the narrow age range (26-36 years) covered. Parameters characterizing topology were better able to distinguish two individuals who demonstrated similar values for scalar measurements (≈ 34% difference, P < 0.001). Whole-section axial stiffness encompassing the cortex was superior at distinguishing two individuals relative to its central subregional TB counterpart (≈ 8% difference; P < 0.05). Interregion comparisons showed that although all parameters were correlated (mean R(2) = 0.78; range 0.57-0.99), the strongest associations observed were those for the erosion index (mean R(2) = 0.95, P ≤ 0.01). CONCLUSION: The reproducibility and structural and mechanical parameter-based discriminative ability achieved in five healthy subjects suggests that 7T-derived µMRI of TB can be applied towards serial patient studies of osteoporosis and may enable earlier detection of disease or treatment-based effects.

Relationship between sodium intensity and perfusion deficits in acute ischemic stroke.

PURPOSE: To assess the relationship between sodium signal intensity changes and oligemia, measured with perfusion-weighted imaging (PWI), in ischemic stroke patients. MATERIALS AND METHODS: Nine ischemic stroke patients (55 ± 13 years), four with follow-up scans, underwent sodium and proton imaging 4-32 hours after symptom onset. Relative sodium intensity was calculated as the ratio of signal intensities in core (identified as hypertintense lesions on diffusion-weighted imaging [DWI]) or putative penumbra (PWI-DWI mismatch) to contralateral homologous regions. RESULTS: Sodium intensity increases in the core were not correlated with the severity of hypoperfusion, measured with either cerebral blood flow (rho = 0.157; P = 0.61) or cerebral blood volume (rho = -0.234; P = 0.44). In contrast, relative sodium intensity was not elevated (4-7 hours 0.96 ± 0.07; 17-32 hours 1.00 ± 0.07) in PWI-DWI mismatch regions. CONCLUSION: Sodium signal intensity cannot be predicted by the degree of hypoperfusion acutely. Sodium intensity also remains unchanged in PWI-DWI mismatch tissue, indicating preservation of ionic homeostasis. Sodium magnetic resonance imaging (MRI), in conjunction with PWI and DWI, may permit identification of patients with viable tissue, despite an unknown symptom onset time.

DWI lesion volume reduction following acute stroke treatment with transient partial aortic obstruction.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) identifies acute cerebral ischemia and DWI lesions are thought to indicate irreversibly damaged areas. However, new evidence suggests that DWI lesions may be reversible, especially with reperfusion. We present a patient who showed substantial reversal of her acute DWI lesion following partial aortic occlusion with Neuroflo™, a novel dual balloon catheter (Neuroflo™, CoAxia, MN). METHODS: Case report/literature review. RESULTS: A 48-year-old woman presented with left-sided weakness and demonstrated an acute DWI lesion in the right middle cerebral artery territory, with diffusion-perfusion mismatch. She was enrolled into an experimental study in which a dual balloon catheter was inflated in the lower aorta. The patient improved and her postprocedure magnetic resonance image showed a significant reduction in lesion volume on diffusion and perfusion-weighted imaging. At 1 month, a repeat computed tomography scan showed a small infarction in the right insula, lentiform nucleus, and frontal cortex. The patient had recovered with no significant disability at her 3-month follow-up. CONCLUSION: Reperfusion can improve DWI lesions. Partial aortic obstruction with a novel dual balloon catheter may be useful to promote reperfusion.

Sodium imaging intensity increases with time after human ischemic stroke.

OBJECTIVE: Establishing time of onset is important in acute stroke management. Current imaging modalities do not allow determination of stroke onset time. Although correlations between sodium magnetic resonance imaging signal intensity within ischemic lesions and time of onset have been shown in animal models, the relation to onset time has not been established in human stroke. Utilizing high-quality sodium images, we tested the hypothesis that sodium signal intensity increases with time from symptom onset in human ischemic stroke. METHODS: Twenty-one stroke patients (63 +/- 15 years old) were scanned 4 to 104 hours after symptom onset. Follow-up images were obtained in 10 patients at 23 to 161 hours after onset, yielding a total of 32 time points. A standard stroke imaging protocol was acquired at 1.5 Tesla, followed by sodium magnetic resonance imaging at 4.7 Tesla. Relative sodium signal intensity within each lesion was measured with respect to the contralateral side. RESULTS: The sodium image quality was sufficient to visualize each acute lesion (lesion volume range, 1.7-217cm(3)). Relative sodium signal intensity increased nonlinearly over time after stroke onset. Sodium images acquired within 7 hours (n = 5) demonstrated a relative increase in lesion intensity of 10% or less, whereas the majority beyond 9 hours demonstrated increases of 23% or more, with an eventual leveling at 69 +/- 18%. INTERPRETATION: Increases of sodium signal intensity within the ischemic lesion are related to time after stroke onset. Thus, noninvasive imaging of sodium may be a novel metabolic biomarker related to stroke progression. Ann Neurol 2009;66:55-62.

Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study.

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).

The relationship between diffusion anisotropy and time of onset after stroke.

Diffusion anisotropy changes in stroke lesions less than 24 h after onset have been reported to be elevated, decreased, or both. To address these mixed findings, we sought to characterize temporal changes of diffusion anisotropy by analyzing anatomically distinct ischemic white matter (WM) regions at 3 time phases within the first 34 h of ischemic stroke onset in 26 stroke patients (2 to 5 h, N=7; 7 to 14 h, N=11; 18 to 34 h, N=8). Mean diffusivity (Trace/3 apparent diffusion coefficient (ADC)), fractional anisotropy (FA), and T2-weighted signal intensity were measured for major and subcortical WM in lesions defined by a >or=30% drop in Trace/3 ADC. Major WM tract lesions with mean decreases of approximately 40% in relative (r) Trace/3 ADC showed an increased rFA of 1.11+/-0.18 (P<0.01) during the hyperacute phase (2 to 5 h), whereas rFA declined to 0.90+/-0.20 (P<0.01) and 0.88+/-0.12 (P<0.01) in the acute (7 to 14 h) and subacute (18 to 34 h) phases, respectively. Of those patients with lesions in major WM, 4 of 8 patients

Neuroprotection from soman-induced seizures in the rodent: evaluation with diffusion- and T2-weighted magnetic resonance imaging.

Exposure to the organophosphate nerve agent soman produces seizures that in turn lead to neuropathology. This study describes the temporal and spatial evolution of brain pathology following soman-induced convulsions and the attenuation of these alterations after neuroprotective intervention with magnetic resonance imaging (MRI). Neuroimaging 12 h after soman exposure, the hippocampus and thalamus exhibited significant decreases (23%) in apparent diffusion coefficients (ADC). These acute effects were resolved by 7 days. In addition, T2 measurements declined significantly at 12 h (37%) returning to near normal values by 24 h. Histopathological analyses confirmed moderate cell loss within the hippocampus and piriform cortex. Together these findings suggest that initial cell death was resolved through regional cellular remodeling. Pharmacological countermeasures were administered in the form of diazepam, a benzodiazepine anticonvulsant, or gacyclidine (GK-11), an anti-glutamatergic compound. Diazepam therapy applied immediately after soman exposure prevented acute ADC changes. However the presence of edema, using T2 measurements, was detected at 3 h within the retrosplenial, amygdala and piriform cortices and at 12 h in the thalamus (34% below normal). GK-11 therapy appeared to prevent most of these changes. However at 7 days after soman, a decrease (17%) in ADC was observed in the piriform cortex. Pathology was confined to the piriform cortex suggesting that this region is more difficult to protect. This is the first report that provides temporal and spatial resolution using MRI with histological correlation of pharmacological interventions against soman-mediated seizure-induced neuropathology.