Biomedical subjects

Julian He

Publications and source records attributed to Julian He.

11 recordsLinked to original sources

PubMed2006

Serial diffusion tensor MRI after transient and permanent cerebral ischemia in nonhuman primates.

BACKGROUND AND PURPOSE: We measured the temporal evolution of the T2 and diffusion tensor imaging parameters after transient and permanent cerebral middle cerebral artery occlusion (MCAo) in macaques, and compared it to standard histological analysis at the study end point. METHODS: Stroke was created in adult male macaques by occluding a middle cerebral artery branch for 3 hours (transient MCAo, n=4 or permanent occlusion, n=3). Conventional MRI and diffusion tensor imaging scans were performed 0 (acute day), 1, 3, 7, 10, 17, and 30 days after MCAo. Animals were euthanized after the final scan and the brains removed for histological analysis. RESULTS: Apparent diffusion coefficient in the lesion was decreased acutely, fractional anisotropy was elevated, and T2 remained normal. Thereafter, apparent diffusion coefficient increased above normal, fractional anisotropy decreased to below normal, T2 increased to a maximum and then declined. Reperfusion at 3 hours accelerated these MRI changes. Only the fractional anisotropy value was significantly different between transient and permanent groups at 30 days. Final MRI-defined fractional lesion volumes were well correlated with corresponding histological lesion volumes. Permanent MCAO animals showed more severe histological damage than their transient MCAO counterparts, especially myelin damage and axonal swelling. CONCLUSIONS: Overall, the MRI evolution of stroke in macaques was closer to what has been observed in humans than in rodent models. This work supports the use of serial MRI in stroke studies in nonhuman primates.

Animals↗

PubMed2006

A nonlinear mesh-warping technique for correcting brain deformation after stroke.

This article presents a warping technique for correcting brain tissue distortion on magnetic resonance imaging (MRI) scans due to stroke lesion growth and for mapping MRI scans to histological sections. Meshes are imposed upon the images for feature specification, and these features are exactly matched in the different images to be mapped, while the other voxels are matched by interpolation. This technique was tested on serial MR images and histological sections that were acquired in a nonhuman primate model of stroke. This technique was able to deliver satisfactory warping results. It is simple and robust and can be utilized in many applications for comparison of multimodality medical images and histological sections.

Algorithms↗

PubMed2006

Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution.

BACKGROUND: An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model. METHODS: Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non-invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil. RESULTS: Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self-feed within 2 hours of recovery. Animals with strokes of >or=4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression. CONCLUSIONS: Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.

Animals↗

PubMed2005

Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain.

PURPOSE: To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. MATERIALS AND METHODS: This study was approved by the Massachusetts General Hospital Subcommittee on Research and Animal Care and the Institutional Animal Care and Use Committee of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton ((1)H) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution (1)H MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed. Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers. RESULTS: During acute infection with SIV, the macaque brain exhibited significant changes in NAA/Cr (P < .02, ANOVA) and synaptophysin (P < .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (r(s) = 0.72, P < .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found. CONCLUSION: NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction.

Animals↗

PubMed2005

Dynamic susceptibility contrast perfusion imaging of cerebral ischemia in nonhuman primates: comparison of Gd-DTPA and NMS60.

PURPOSE: To study a new gadolinium (Gd) contrast agent-NMS60-for MR perfusion-weighted imaging (PWI) of brain tissue. MATERIALS AND METHODS: NMS60 is a Gd3+ trimer with a molecular weight of 2158 Daltons, and a T2 relaxivity almost three times higher than that of Gd-DTPA. Middle cerebral artery (MCA) occlusion was induced in nine nonhuman primates. The animals were scanned acutely and for up to six follow-up time points. PWI peak, and time-to-peak maps were generated, and perfusion deficit volumes were measured from these maps. The values of peak, time-to-peak, and perfusion deficit volume were compared between NMS60 and GD-DTPA. RESULTS: These results demonstrate that there was no significant difference in our calculated perfusion parameters between the two contrast agents. CONCLUSION: The two agents were found to be equally effective for PWI for acute and chronic stroke in primates. Along with its previously demonstrated advantage for T1-enhanced imaging, the current results show that NMS60 is a viable contrast agent for use in stroke patients.

Animals↗

PubMed2005

Comparisons of brain metabolites observed by HRMAS 1H NMR of intact tissue and solution 1H NMR of tissue extracts in SIV-infected macaques.

The objective of this study was to compare ex vivo proton high-resolution magic angle spinning magnetic resonance spectra of intact tissue with those spectra obtained by solution (1)H NMR of brain extracts of the same sample. Sixteen brain tissue samples from simian immunodeficiency virus-infected rhesus macaques from both frontal cortex and putamen were evaluated by comparing brain metabolite quantities of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (MI), creatine (Cr), lactate (Lac), glutamate (Glu) and acetate (Ace). The ratios of the individual NMR peak areas of all metabolites relative to the creatine peak area were calculated. Linear regression analysis revealed significant correlations between measurements using the two methods. The strength of the correlations varied depending on the metabolite studied. We found highly significant correlations for NAA/Cr (r2 = 0.77; p < 0.0001), NAA + Ace/Cr (r2 = 0.73; p < 0.0001) and MI/Cr (r2 = 0.75; p < 0.0001). We observed somewhat less strong correlations for Glu/Cr (r2 = 0.54; p < 0.002) and Lac/Cr (r2 = 0.54; p < 0.002). There was a substantially weaker correlation for Cho/Cr (r2 = 0.32; p = 0.02). When plotting the metabolite ratios obtained by 1H HRMAS NMR of the intact tissue sample on the ordinate vs 1H NMR of the tissue extract on the abscissa, most metabolites exhibited a slope close to unity, and a positive intercept probably due to macromolecular contributions to the MAS spectra. The slope for Cho/Cr was substantially less than unity. Generally, samples from the frontal cortex showed a better correlation between intact and extracted tissue samples than putamen. This is most prominent in the cases of NAA/Cr and Cho/Cr. We conclude that both methods provide substantially the same information for most major brain metabolites, with the exception of the Cho resonance.

Animals↗

PubMed2004

A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS.

BACKGROUND: The neurological complications of HIV infection remain poorly understood. Clinically, in vivo 1H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS. RESULTS: Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and 1H MRS to terminal AIDS or the endpoint of 2 years. During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex. Subsequently, brain metabolic patterns diverged between animals. There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022). Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation. However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P < 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P < 0.02, R = -0.73). No MRI abnormalities were detected at any time. CONCLUSIONS: After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load. An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis. Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection. Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection. These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the CNS.

AIDS Dementia Complex↗

PubMed2004

In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS.

The metabolic response of the rhesus macaque brain during acute simian immunodeficiency virus (SIV) infection was investigated with in vivo (1)H MR spectroscopy. Fifteen rhesus macaques were studied before inoculation, and once or twice after infection. In all, 13/15 macaques had elevations of Cho/NAA at 11-13 days postinoculation (dpi); all 10 macaques measured after 13 dpi had subsequent reduction of this ratio (ANOVA, P < 10(-6)). There were significant increases in Cho/Cr (20%, P = 0.04) and MI/Cr (14%, P = 0.003) at 11 dpi. At 13 dpi a 7.7% decrease (P = 0.02) in NAA/Cr was observed, while Cho/Cr was no longer significantly different from baseline. At 27 dpi Cho/Cr was decreased to 18% (P = 0.004) below preinoculation values, while NAA/Cr and MI/Cr were at baseline values. Absolute concentrations of Cho, MI, and NAA showed a similar time course, with no observed changes in Cr. There was a strong correlation between Cho/Cr change and plasma viral load (r(s) = 0.79, P < 0.01). Acute SIV produces extensive metabolic abnormalities in the brain, which may reflect inflammation and neuronal injury, which are reversed with immunological control of the virus. Similar events are likely to occur in acutely HIV-infected people, and may explain the neurobehavioral symptoms associated with acute HIV infection.

AIDS Dementia Complex↗

PubMed2003

Assessing tissue viability with MR diffusion and perfusion imaging.

BACKGROUND AND PURPOSE: Diffusion- (DW) and perfusion-weighted (PW) MR imaging reflect neurophysiologic changes during stroke evolution. We sought to determine parameters that distinguish regions of brain destined for infarction from those that will survive despite hypoperfusion. METHODS: DW and PW images were obtained in 30 patients at 1-12 hours after symptom onset. Relative cerebral blood volume (rCBV), flow (rCBF), mean transit time (MTT), apparent diffusion coefficient (ADC), DW image signal intensity, and fractional anisotropy (FA) lesion-contralateral normal region ratios were obtained in the following regions: 1) infarct core with hyperintensity on DW image, abnormality on rCBF and MTT images, and follow-up abnormality; 2) infarcted penumbra with normal DW image, abnormal rCBF and MTT images, and follow-up abnormality; and 3) hypoperfused tissue that remained viable, with normal DW image, abnormal rCBF and MTT images, and normal follow-up. RESULTS: rCBF ratios for regions 1, 2, and 3 were 0.32 +/- 0.11, 0.46 +/- 0.13, and 0.58 +/- 0.12, respectively, and were significantly different. DW image intensity and ADC ratios were significantly different among all regions, but were more similar than rCBF ratios. rCBV and FA ratios were not significantly different between regions 2 and 3. No MTT ratios were significantly different. No region of interest with an rCBF ratio less than 0.36, an rCBV ratio less than 0.53, an ADC ratio less than 0.85, a DW image intensity ratio greater than 1.23, or an FA ratio greater than 1.10 remained viable. No region of interest with an rCBF ratio greater than 0.79 infarcted. CONCLUSIONS: Differences among mean ratios of three regions investigated were greatest for the rCBF ratio. The rCBF ratio may be the most useful parameter in differentiating viable tissue that is likely to infarct without intervention, from tissue that will survive despite hypoperfusion. ADC, DW intensity, FA, and rCBV ratios may provide adjunctive information.

Adult↗

PubMed2002

CT and conventional and diffusion-weighted MR imaging in acute stroke: study in 691 patients at presentation to the emergency department.

PURPOSE: To compare the diagnostic accuracy of computed tomography (CT) and magnetic resonance (MR) imaging in a consecutive series of patients at presentation to the emergency department with symptoms of acute stroke. MATERIALS AND METHODS: Clinical data and images obtained in 691 consecutive patients with suspected acute stroke were examined. Results of first and second head CT and brain diffusion-weighted (DW) and conventional MR imaging were compared with each other and with the final neurologic discharge diagnosis. RESULTS: Five hundred seventy-three patients underwent CT at presentation, with 42% sensitivity (95% CI: 37%, 46%) and 91% specificity (95% CI: 82%, 96%). A total of 173 patients underwent a second CT examination, with 77% sensitivity (95% CI: 70%, 84%) and 79% specificity (95% CI: 49%, 95%). Of 498 MR images, 411 were DW, with 94% sensitivity (95% CI: 1%, 96%) and 97% specificity (95% CI: 88%, 100%), and 87 were conventional, with 70% sensitivity (95% CI: 58%, 81%) and 94% specificity (95% CI: 70%, 100%). By using DW MR imaging in the early period (<6 hours after presentation to emergency department), a 97% sensitivity (95% CI: 92%, 100%) and a 100% specificity (95% CI: 69%, 100%) were achieved, compared with 58% (29%-84%) and 100% (16%-100%), respectively, with conventional MR imaging, and 40% (35%-45%) and 92% (84%-97%), respectively, with CT. Negative predictive value was higher with DW MR imaging (73%) than with conventional (42%) MR imaging or CT (24%). In studies conducted within 12 hours, DW MR imaging achieved substantially superior accuracy than did CT. After 12 hours, accuracy was equivalent. CONCLUSION: In the diagnosis of stroke in the early period (<12 hours after presentation), DW MR imaging is superior to conventional MR imaging and CT.

Acute Disease↗

PubMedDate not supplied

Predicting cerebral ischemic infarct volume with diffusion and perfusion MR imaging.

BACKGROUND AND PURPOSE: Diffusion and perfusion MR imaging have proved useful in the assessment of acute stroke. We evaluated the utility of these techniques in detecting acute ischemic infarction and in predicting final infarct size. METHODS: Diffusion and hemodynamic images were obtained in 134 patients within a mean of 12.3 hours of onset of acute ischemic stroke symptoms. We retrospectively reviewed patient radiology reports to determine the presence or absence of lesion identification on initial diffusion- (DW) and perfusion-weighted (PW) images. Radiologists were not blinded to the initial clinical assessment. For determination of sensitivity and specificity, the final discharge diagnosis was used as the criterion standard. Neurologists were not blinded to the DW or PW imaging findings. In 81 patients, acute lesions were compared with final infarct volumes. RESULTS: Sensitivities of DW imaging and cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) perfusion parameters were 94%, 74%, 84%, and 84%, respectively. Specificities of DW imaging, CBV, CBF, and MTT were 96%, 100%, 96%, and 96%, respectively. Results were similar in 93 patients imaged within 12 hours. In 81 patients with follow-up, regression analysis yielded r(2) = 0.9, slope = 1.24 for DW imaging; r(2) = 0.84, slope = 1.22 for CBV; r(2) = 0.35, slope = 0.44 for CBF; and r(2) = 0.22, slope = 0.32 for MTT, versus follow-up volume. A DW-CBV mismatch predicted additional lesion growth, whereas DW-CBF and DW-MTT mismatches did not. Results were similar in 60 patients imaged within 12 hours. CONCLUSION: Diffusion and hemodynamic images are sensitive and specific for detecting acute infarction. DW imaging and CBV best predict final infarct volume. DW-CBV mismatch predicts lesion growth into the CBV abnormality. CBF and MTT help identify additional tissue with altered perfusion but have lower correlation with final volume.

Adult↗