Compartmental study of diffusion and relaxation measured in vivo in normal and ischemic rat brain and trigeminal nerve

Does, Mark D.; Gore, John C.

doi:10.1002/1522-2594(200006)43:6<837::aid-mrm9>3.0.co;2-o

Cited by 62 publications

(63 citation statements)

References 39 publications

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“…Regional cerebral blood flow studies were not done in this work and may have potentially provided helpful insight into the neuroprotective effect of BB-1101. In this study, the absolute ADC values obtained for healthy rat brain tissue are higher than those found in the literature (ADC values for healthy rat brain tissue are in the range 0.6 to 0.7 Â 10 À3 mm 2 /sec) (Does and Gore, 2000). One possible explanation for this finding would be motion-induced artefact during data acquisition.…”

Section: Bb1101contrasting

confidence: 75%

Early Beneficial Effect of Matrix Metalloproteinase Inhibition on Blood—Brain Barrier Permeability as Measured by Magnetic Resonance Imaging Countered by Impaired Long-Term Recovery after Stroke in Rat Brain

Sood

Taheri

Candelario‐Jalil

et al. 2007

J Cereb Blood Flow Metab

102

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Proteolytic disruption of the extracellular matrix with opening of the blood-brain barrier (BBB) because of matrix metalloproteinases (MMPs) occurs in reperfusion injury after stroke. Matrix metalloproteinase inhibition blocks the early disruption of the BBB, but the long-term consequences of short-term MMP inhibition are not known. Recently, a method to quantify BBB permeability by graphical methods was described, which provides a way to study both early disruption of the BBB and long-term effects on recovery in the same animal. We used a broad-spectrum MMP inhibitor, BB1101, to determine both the usefulness of the Magnetic resonance imaging (MRI) method for treatment studies and the long-term effects on recovery. Magnetic resonance imaging studies were performed in control (N = 6) and drug-treated (N = 8) groups on a dedicated 4.7-T MRI scanner. Adult Wistar-Kyoto underwent a 2-h middle cerebral artery occlusion followed by an MRI study after 3 h of reperfusion, which consisted of T2-and diffusion-weighted techniques. Additionally, a rapid T1 mapping protocol was also implemented to acquire one pre-gadolinium-diethylenetriaminepentaacetic acid baseline data set followed by postinjection data sets at 3-min intervals for 45 mins. The same animal was imaged again at 48 h for lesion size estimation. Data was postprocessed pixel-wise to generate apparent diffusion coefficient and permeability coefficient maps. Treatment with BB-1101 significantly reduced BBB permeability at 3 h, but failed to reduce lesion size at 48 h. Behavioral studies showed impairment in recovery in treated rats. Magnetic resonance imaging allowed for the monitoring of multiple parameters in the same animal. Our studies showed that BB-1101 was an excellent inhibitor of the BBB damage. However, results show that BB-1101 may be responsible for significant deterioration in neurologic status of treated animals. Although these preliminary results suggest that BB-1101 is useful in reducing early BBB leakage owing to reperfusion injury in stroke, further studies will be needed to determine whether the later detrimental effects can be eliminated by shorter time course of drug delivery.

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Section: Bb1101contrasting

confidence: 75%

Early Beneficial Effect of Matrix Metalloproteinase Inhibition on Blood—Brain Barrier Permeability as Measured by Magnetic Resonance Imaging Countered by Impaired Long-Term Recovery after Stroke in Rat Brain

Sood

Taheri

Candelario‐Jalil

et al. 2007

J Cereb Blood Flow Metab

102

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“…Carano et al (2000) reported an acute elevation of FA in subcortical and cortical regions (B20% rise) as early as 1 h after middle cerebral artery occlusion in rats, with a progressive decline of B25% to 40% noted by 3 h up to 5 days after stroke. In another study, Does and Gore (2000) suggested that diffusion anisotropy is slightly elevated 10 mins post mortem in the trigeminal nerve of a 'global ischemia' rat model. In their study, greater reductions in ADC values measured perpendicular to the nerve (26% to 31% drops) relative to ADC values measured parallel to the nerve (14% to 19% drops) accounted for the increased anisotropy.…”

Section: Discussionmentioning

confidence: 97%

The Relationship between Diffusion Anisotropy and Time of Onset after Stroke

Bhagat

Emery

Shuaib

et al. 2006

J Cereb Blood Flow Metab

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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 Z30% drop in Trace/3 ADC. Major WM tract lesions with mean decreases of B40% in relative (r) Trace/3 ADC showed an increased rFA of 1.1160.18 (P < 0.01) during the hyperacute phase (2 to 5 h), whereas rFA declined to 0.9060.20 (P < 0.01) and 0.8860.12 (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 < -7 h showed elevated rFA as opposed to none of the remaining 13 patients after 7 h. A greater proportion of the evaluated WM regions-of-interest (ROI) in the hyperacute phase revealed increases in rFA (60%), whereas conversely large proportions of ROIs (55% and 59%) in the acute and subacute phases showed reduced rFA. Similar anisotropy changes were noted in subcortical WM regions in the gyri.

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“…8 and 9, both longitudinal and transverse relaxation have been observed to be monoexponential (27,28), so the TRs and TEs should not bias the measurement toward one compartment or another. In the diffusion-weighting domain, the signal decay is known to be non-monoexponential (13), although the physical origin of this decay characteristic is not clear.…”

Section: Discussionmentioning

confidence: 99%

Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain

Does

Parsons

Gore

2003

Magnetic Resonance in Med

Self Cite

213

326

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Oscillating gradients were used to probe the diffusion-time/ frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 s, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known microanatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 m, similar to a typical cellular dimension in gray matter. Magn Reson Med 49:206 -215, 2003. © 2003 Wiley-Liss, Inc. Key words: MRI; diffusion; restriction; ischemia; oscillating gradientWhen the Brownian motion of a molecule is physically impeded or hindered, its effective rate of self-diffusion, or apparent diffusion coefficient (ADC), is reduced, and the diffusion is said to be restricted. In tissues, restriction is thought to be a significant mechanism affecting contrast in diffusion-weighted imaging, in both normal and pathological states. In particular, restriction of water by cell membranes is believed to be the dominant mechanism causing diffusion anisotropy in the nervous system (1), and it has also been postulated to play a central role in the marked decline of water ADC in neural tissue following the onset of ischemia (2-4). However, due to hardware limitations, there has been limited direct investigation in vivo of the effects of restrictions on diffusion measurements with MRI. Such observations can be made by measuring ADC as a function of diffusion time.In an NMR diffusion measurement, if the time allowed for spins to migrate is brief enough, restriction will have little impact on the measurement and the ADC will closely reflect the intrinsic diffusion coefficient. As the diffusion time increases and the molecules interact more often with the physical restrictions, the ADC declines toward an asymptotic value. Several such measurements have been made on excised tissue samples (5-9), typically using spectrometers equipped with strong gradients (50 -500 gauss/cm), which allow ADC measurements at relatively short diffusion times.In vivo measurements, however, have been limited by gradient strengths that are typically one or two orders of magnitude smaller, making the minimal diffusion time relatively long. In RIF-1 tumors, Helmer et al. (10) fou...

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Compartmental study of diffusion and relaxation measured in vivo in normal and ischemic rat brain and trigeminal nerve

Cited by 62 publications

References 39 publications

Early Beneficial Effect of Matrix Metalloproteinase Inhibition on Blood—Brain Barrier Permeability as Measured by Magnetic Resonance Imaging Countered by Impaired Long-Term Recovery after Stroke in Rat Brain

Early Beneficial Effect of Matrix Metalloproteinase Inhibition on Blood—Brain Barrier Permeability as Measured by Magnetic Resonance Imaging Countered by Impaired Long-Term Recovery after Stroke in Rat Brain

The Relationship between Diffusion Anisotropy and Time of Onset after Stroke

Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain

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