MRI of spontaneous fluctuations after acute cerebral ischemia in nonhuman primates.

PURPOSE: To study the spontaneous low-frequency blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal fluctuations during hyperacute focal cerebral ischemia. MATERIALS AND METHODS: A stroke model in nonhuman primates (macaques) was used in this study. Spontaneous fluctuations were recorded using a series of gradient-recalled echo (GRE) echo-planar imaging (EPI) images. Fast Fourier transformation (FFT) was performed on the serial EPI data to calculate the frequency and magnitude of the spontaneous fluctuations. Diffusion tensor imaging (DTI) and perfusion-weighted imaging (PWI) were preformed to detect the ischemic lesion. RESULTS: The frequency of these fluctuations decreased in the periinfarct tissue in the ipsilateral hemisphere, while their magnitude increased. This area of abnormal signal fluctuations often extended beyond the hyperacute diffusion/perfusion abnormality. CONCLUSION: This study suggests that measurement of the spontaneous fMRI signal fluctuations provides different information than is available from diffusion/perfusion or T2-weighted MRI.

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.

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.

Pig kidney transplantation in baboons treated intravenously with a bovine serum albumin-Galalpha1-3Gal conjugate.

The maintenance of depletion of antibody (Ab) reactive with Galalpha1-3Gal (Gal) on pig vascular endothelial cells by the intravenous (i.v.) infusion of a synthetic Gal conjugate has been proposed as a means of delaying Ab-mediated rejection of transplanted pig organs in primates. We have therefore studied the effect of the continuous i.v. infusion of bovine serum albumin conjugated to multiple synthetic Gal type 6 oligosaccharides (BSA-Gal) on anti-Gal Ab levels and on graft survival in baboons undergoing pig kidney transplantation. Group 1 baboons (n=3) underwent extracorporeal immunoadsorption of anti-Gal Ab, a cyclophosphamide (CPP)-based immunosuppressive regimen, and a non-transgenic pig kidney transplant. Group 2 (n=2) were treated identically to Group 1 but, in addition, received a continuous i.v. infusion of BSA-Gal. Group 3 (n=2) were treated identically to Group 2, but without CPP. A single baboon (Group 4) underwent extracorporeal immunoadsorption, a CPP-based regimen, and continuous i.v. BSA-Gal therapy for 28 days, but did not receive a pig kidney transplant. Two of the transplanted pig kidneys in Group 1 were excised on post transplant days 7 and 13 for a rejected ureter, and disseminated intravascular coagulation (DIC), respectively. The third baboon died of sepsis on day 6. All transplanted ureters and kidneys showed some histopathologic features of acute humoral xenograft rejection. Group 2 baboons were euthanized on days 8 and 11, respectively, for liver failure. At autopsy, there were histopathological features of widespread liver necrosis, but the pig kidneys and ureters showed no features of rejection. The pig kidneys in Group 3 baboons were excised for renal vein thrombosis (day 9) and DIC (day 12); there was no histological signs of rejection in the pig kidneys or ureter, although there were focal areas of modest liver injury in one baboon on biopsy. The single Group 4 baboon showed no biochemical or histological features of liver injury. Anti-Gal Ab levels returned in Group 1, but were maintained at negligible levels in the baboons in Groups 2 to 4 that received BSA-Gal therapy. Continuous i.v. therapy with BSA-Gal is largely successful in maintaining depletion of circulating anti-Gal antibodies and in preventing or delaying Ab deposition and acute humoral xenograft rejection in porcine grafts, but may be associated with liver injury when administered in the presence of a pig kidney transplant and CPP therapy. The mechanism of the hepatic injury remains uncertain.