Biomedical subjects

Donald S Williams

Publications and source records attributed to Donald S Williams.

7 recordsLinked to original sources

PubMed2006

Differences between arterial occlusive and cortical photothrombosis stroke models with magnetic resonance imaging and microtubule-associated protein-2 immunoreactivity.

The differences between two models of cerebral ischemia [middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT)] were explored with multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity sections aligned with the MR images in the same coronal plane were used to map the infarct and to guide region-of-interest selection. In ischemic cortex, the larger T1 increase in PT versus MCAT (42+/-7% vs. 16+/-5%) is related to the different character of edema between these models; yet, neither CBF nor ADCtr discriminated between them at 3.5 h, suggesting that different mechanisms of ischemic damage to the brain cells resulted in the same ADCtr value. CBF and ADCtr were depressed in immediately adjacent ischemic border by 27+/-7% and 47+/-10%, respectively, in MCAT but not in PT, suggesting marginal perfusion in MCAT. CBF in homotopic normal cortex in the opposite hemisphere was higher for PT compared with MCAT (199+/-20 and 134+/-10 ml/100 g/min, respectively). Different pathological processes in the two models affect CBF, ADCtr and T1 in a unique, regionally specific manner. The PT model differs substantially from the MCAT and is not a model of cortical ischemia with an appreciable border zone.

Animals↗

PubMed2006

Quantitative perfusion imaging using arterial spin labeling.

MRI-based perfusion imaging techniques can be classified into those that use exogenously administered contrast agents and those that use an endogenous material that reflects blood flow. This chapter focuses on the technique of arterial spin labeling (ASL), in which endogenous water is made a freely diffusible perfusion tracer by perturbing the magnetization of blood water in arteries prior to their entry into tissue of interest. The technique is totally noninvasive and allows repeated quantitative blood flow measurements in a time scale limited only by the spin lattice relaxation time (T1). Absolute quantitation requires measurement of T1, transit time, and labeling efficiency, as well as careful control for magnetization transfer effects. Two main variants of the ASL technique are in use: continuous ASL (CASL) and pulsed ASL (PASL). This chapter describes basic theory for CASL, and experimental and computational procedures for obtaining quantitative perfusion maps of the brain. Extension of the technique for renal perfusion imaging is outlined.

Animals↗

PubMed2006

The role of MRI and PET/SPECT in Alzheimer's disease.

Alzheimer's disease (AD) is difficult to diagnose in its early stages, and even if detected early, there is no preventative treatment. Imaging modalities such as MRI, PET, and SPECT have the potential to contribute to both the diagnosis of Alzheimer's disease, as well as assist in the search for more effective treatments. A number of AD-related biomarkers have been proposed and evaluated. The use of PET imaging to detect alterations in regional brain metabolism using [(18)F]FDG has enabled more sensitive and accurate early diagnosis of AD, especially in conjunction with traditional medical evaluation. Additionally, magnetic resonance imaging and spectroscopy provide a wide range of biomarkers that have been shown to correlate with the progression of AD. Some of these markers have been pursued in clinical trials. Progress has been made toward the evaluation of other more AD-specific biomarkers. However, many questions remain concerning the validity and sensitivity of these imaging biomarkers to aid in the assessment of potential new treatments, especially those related to increased levels of amyloid peptides in the brain.

Alzheimer Disease↗

PubMed2004

Normal and transplanted rat kidneys: diffusion MR imaging at 7 T.

PURPOSE: To investigate the feasibility of obtaining reproducible apparent diffusion coefficient (ADC) maps of normal rat kidneys by using respiratory-triggered spin-echo diffusion-weighted magnetic resonance (MR) imaging, to investigate the sensitivity of ADC maps in the evaluation of renal blood flow, and to use this technique to monitor acute graft rejection in transplanted rat kidneys. MATERIALS AND METHODS: Spin-echo diffusion-weighted MR imaging measurements were performed in 20 normal rats and nine rats that had undergone transplantation (six rats had received allografts; three had received isografts) at 7 T. To evaluate the effect of alteration in blood flow and water transport function, angiotensin II was infused in six normal rats and a series of spin-echo diffusion-weighted MR images was obtained at five time points. Transplanted kidneys were monitored by obtaining spin-echo diffusion-weighted MR images and gradient-echo MR images every 2 hours for 8 hours on postoperative day 4. Statistical analysis was performed with repeated-measures multivariate analysis of variance and the paired t test. RESULTS: No significant differences in ADC values were observed between right and left kidneys in all three orthogonal directions; however, a small difference was observed between the cortex and medulla. ADC values in the cephalocaudal and mediolateral directions were higher than those in the anteroposterior direction (P <.01 for all). ADC values in the cortex and medulla decreased significantly (by >35%, P <.01) during angiotensin II-induced reduction in renal blood flow. No significant signal intensity change was observed between native and transplanted kidneys on gradient-echo MR images. Allografts exhibited decreased ADC values (P <.01) and isografts exhibited similar ADC values compared with native kidneys. CONCLUSION: These findings suggest that reproducible renal ADC maps can be obtained in rats by using spin-echo diffusion-weighted MR imaging at 7 T. Spin-echo diffusion-weighted MR imaging may have potential as a noninvasive tool for monitoring early graft rejection after kidney transplantation.

Angiotensin II↗

PubMed2002

MRI of lungs using partial liquid ventilation with water-in-perfluorocarbon emulsions.

A novel (1)H-MRI contrast modality for rat lungs has been developed using water-in-perfluorocarbon (PFC) emulsions for partial liquid ventilation (PLV). The feasibility of the new ventilation protocol for (1)H-MRI studies of lungs has been demonstrated. (1)H-MR images of lungs have been obtained with sensitivity and spatial resolution higher than those of the (19)F-MRI of lungs previously reported. Diffusion-weighted MRI measurements of lungs showed that the results obtained are related to the pulmonary architecture and functional properties of lungs. Although the methodology needs further improvement and evaluation, it appears to have great potential in a wide range of new applications in the field of lung MRI, such as in vivo detection of lung cancer, emphysema, and allograft rejection following lung transplantation. The ability of this technique to achieve high-quality MR images of lungs, together with its technical simplicity, stability, and low cost, makes this method a promising imaging technique for the lungs.

Animals↗

PubMed2002

In vivo detection of acute rat renal allograft rejection by MRI with USPIO particles.

BACKGROUND: Magnetic resonance imaging (MRI) for non-invasively detecting renal rejection was developed by monitoring the accumulation of macrophages labeled with dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) particles at the rat renal allografts during acute rejection. METHODS: Five groups of male rats with DA-->BN renal allografts and one group with BN-->BN renal isografts were investigated by MRI before, immediately after, and 24 hr after intravenous infusion with different doses of USPIO particles. All infusions were done on post-operative day 4. MRI experiments were carried out in a 4.7-Tesla instrument using a gradient echo sequence. RESULTS: MR signal intensity (MRSI) of the cortex was found to decrease with higher dosages of USPIO particles. In the absence of USPIO infusion, a decrease in MRSI was seen in the medulla region, presumably due to hemorrhage associated with renal graft rejection, while no significant change was observed in the cortex. The optimal dose of USPIO particles for visualizing rejection-associated changes in our rat kidney model appears to be 6 mg Fe/kg body weight. Iron staining results correlated with the MRSI data, indicating that the signal reduction in the MR images was due to the presence of iron. Immunohistochemical results indicated that USPIO particles were mostly taken up by infiltrating macrophages in the rejecting grafts. CONCLUSIONS: Our results suggest that MRI with intravenous administration of dextran-coated USPIO particles appears to be a valuable and promising tool that can be used as a non-invasive and sensitive method to detect graft rejection in renal transplantation.

Acute Disease↗

PubMed2002

Cerebral blood flow at one year after controlled cortical impact in rats: assessment by magnetic resonance imaging.

Progressive tissue loss and delayed cognitive deficits are seen in rats during the initial year after experimental traumatic brain injury (TBI). As much as 10% of parenchymal volume is lost even in the contralateral hemisphere by 1 year after controlled cortical impact (CCI) in rats. Progressive declines in cerebral blood flow (CBF) are also associated with advanced age and neurodegenerative diseases. Surprisingly, the long-term effects of TBI on CBF remain undefined. CBF was quantified by continuous arterial spin-labeled magnetic resonance imaging (MRI) and measurements of spin-lattice relaxation time in a slice through the plane of injury at 1 year after experimental TBI produced by CCI (n = 4) or sham surgery (n = 4) in rats. CBF was quantified in six regions of interest (ROIs) that were anatomically identified on the control images in each hemisphere and included a medial cortical segment (contusion-enriched, beneath the impact site, on the ipsilateral side) cortex, hippocampus, thalamus, amygdala/pyriform cortex, and hemisphere. At 1 year after injury, CBF was dramatically (96%) reduced in structures within the large cystic lesion that was seen in three of four rats and variably included cortex and hippocampus. Overall, there was an 80% reduction in CBF in the ipsilateral medial cortical segment comparing CCI and sham groups. Similarly, 52% and 67% reductions were seen in CBF in the cortical and hippocampal ROIs ipsilateral to impact (CCI vs. sham), respectively. These are regions both with marked CBF disturbances early after injury and that ultimately suffer considerable tissue loss over the 1-year interval. However, at 1 year after CCI, CBF was not different from sham in other ROIs, including ipsilateral thalamus, or either contralateral hippocampus or hemisphere. We conclude that, at 1 year after CCI, CBF is reduced in anatomic structures at or near the impact site, including injured cortex and hippocampus, and this translates into a reduction in hemispheric CBF. However, despite both significant occult tissue loss ipsilateral and contralateral to the injury and delayed cognitive deficits, widespread reductions in CBF are not observed. This suggests the possibility of remodeling or repackaging of the brain that preserves CBF outside of the cystic lesion.

Animals↗