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Biomedical subjects

R J Ordidge

Publications and source records attributed to R J Ordidge.

At least 37 records · Page 2Linked to original sources

Frequency offset corrected inversion (FOCI) pulses for use in localized spectroscopy.

Gradient localized spectroscopy techniques suffer from a well documented spatial localization error caused by the difference in chemical shifts between resonances. This results in the acquisition of spectra from partially overlapping spatial regions of the sample, with each resonance representing a different region. The image-selected in vivo spectroscopy technique uses hyperbolic secant inversion pulses, where the main limitation in reducing this error is in the RF power available for application of the selective RF pulse. This spatial localization error may be dramatically reduced by increasing, and temporally shaping, the gradient pulse during slice-selective spin inversion. The performance of these RF pulses have been experimentally verified.

Magnetic Resonance Spectroscopy↗

Preliminary observations of transverse relaxation rates obtained at 3 tesla from the substantia nigra of adult normal human brain.

The transverse relaxation rates R2 and R2* were measured at 3 T in the substantia nigra of the midbrain of adult normal human controls. The relaxation rate arising from magnetic inhomogeneities, R2', was calculated from the relationship R2* = R2 + R2'. No significant differences were found for any parameters between left and right side substantia nigra regions, however, a significant inverse correlation was found between R2 and R2' (r = 0.70, p = 0.035). Water diffusion, in the presence of paramagnetic metal ions, may play a role in determining the relative contributions to reversible and irreversible transverse relaxation and may explain the inverse correlation demonstrated here.

Aged↗

Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease.

Elevated iron levels in the substantia nigra (SN) of the brain in Parkinson's disease (PD) may mediate lipid peroxidative reactions, promoting SN neuronal death. To assess SN iron accumulation in living PD patients and its relation to motor performance, we measured, in 13 nondemented PD patients and 10 normal control subjects, simple reaction time (SRT) and simple movement time (SMT), followed by head MRI in a 3-tesla system. We measured T2 and T2* in the right and left SN of all subjects and calculated R2', the relaxation rate due to local magnetic field in-homogeneities, from these values. Asymmetries of 1/T2 (R2), 1/T2* (R2*), or R2' versus asymmetries of SRT and SMT were assessed in eight PD subjects who had not taken anti-PD medication(s) for 12 hours. The average of right and left SN values for R2 was lower, and R2* and R2' were higher, in PD patients than in controls (R2, p = 0.046; R2*, p = 0.001; R2', p < 0.001). R2' best predicted group differences. The asymmetry of SRT performance was highly correlated with asymmetries of SN R2* (0.91; p = 0.001) and R2' (0.72; p = 0.03). These results strongly suggest that the increases in iron levels seen postmortem in the SN in PD are reflected in increased iron-related MRI contrast at 3 tesla in living PD patients. Correlations with motor performance in PD suggest that the clinical severity of PD may be related to SN iron accumulation.

Adult↗

Assessment of relative brain iron concentrations using T2-weighted and T2*-weighted MRI at 3 Tesla.

In this paper a new method is presented for the relative assessment of brain iron concentrations based on the evaluation of T2 and T2*-weighted images. A multiecho sequence is employed for rapid measurement of T2 and T2*, enabling calculation of the line broadening effect (T2'). Several groups have failed to show a correlation between T2 and brain iron content. However, quantification of T2', and the associated relaxation rate R2', may provide a more specific relative measure of brain iron concentration. This may find application in the study of brain diseases, which cause associated changes in brain iron levels. A new method of field inhomogeneity correction is presented that allows the separation of global and local field inhomogeneities, leading to more accurate T2* measurements and hence, T2' values. The combination of T2*, and T2-weighted MRI methods enables the differentiation of Parkinson's disease patients from normal age-matched controls based on differences in iron content within the substantia nigra.

Aged↗

A low flip angle spin-echo technique for producing rapid diffusion weighted MR images.

A method is described for producing rapid diffusion-weighted images using a modified low flip angle imaging technique. Utility of the method is demonstrated by the quantification of diffusion coefficients in a rat model of focal ischemia. The method may be readily applied to animal research studies using NMR research systems with modest gradient capabilities.

Animals↗

Correction of motional artifacts in diffusion-weighted MR images using navigator echoes.

Patient motion can seriously degrade the quality of diffusion-weighted MR images obtained using standard 2DFT imaging procedures. The main source of error arises from an MR signal phase-shift error which is proportional to the magnitude of the motion. A modified pulse sequence is proposed which uses the phase information from an additional spin echo to correct for patient motion. Application of this technique is demonstrated for a human brain study, which greatly improves the quantification of diffusion values from regions of brain tissue.

Artifacts↗

The effect of hypothermia on transient focal ischemia in rat brain evaluated by diffusion- and perfusion-weighted NMR imaging.

The effect of moderate whole-body hypothermia (30 degrees C) on transient middle cerebral artery (MCA) occlusion in the rat was evaluated using diffusion- and perfusion-weighted magnetic resonance imaging. Two hours of transient MCA occlusion was induced by intracarotid insertion of a nylon filament under normothermic (n = 14) and hypothermic (n = 7) conditions. Diffusion- and perfusion-weighted imaging were performed before, during, and after focal ischemia from 30 min up to 7 days. In hypothermic animals, scattered neuronal necrosis was localized to select areas of the caudate putamen and the parietal and insular cortex. In contrast, the normothermic ischemic animals exhibited pan-necrosis and infarct encompassing the damaged area. The diffusion and perfusion data measured from caudate putamen indicate that hypothermia causes a significant reduction in the apparent diffusion coefficient of water (ADCw) and CBF values from normothermic control values (p < 0.01). In both normothermic and hypothermic animals after onset of MCA occlusion, ADCw and CBF values in the core of the ischemic region (striatum) significantly declined from the preischemic and homologous contralateral control ADCw and CBF values (p < 0.05). However, ADCw and CBF in the hypothermic group returned toward control more rapidly than in the normothermic group. These results suggest that the protective effect of hypothermia on ischemic cell damage is reflected in the early return of ADCw during reperfusion and the reduction of ischemic cell damage by hypothermia may be mediated by the improved CBF during acute reperfusion.

Animals↗

Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats.

BACKGROUND AND PURPOSE: This study was performed to document the progression of ischemic brain damage after middle cerebral artery occlusion in the rat using magnetic resonance imaging and histopathologic methods. METHODS: Cerebral ischemia was induced through permanent tandem occlusion of ipsilateral middle cerebral and common carotid arteries. The evolution of magnetic resonance imaging and histopathologic parameter changes was studied, both short term (1.5 to 8 hours) and long term (24 to 168 hours), in five specific brain regions within the middle cerebral artery territory. RESULTS: Significant changes in proton nuclear magnetic resonance spin-lattice and spin-spin relaxation times and the "apparent" diffusion coefficient of water could be detected within hours after the onset of permanent focal cerebral ischemia, whereas significant alterations in proton spin-density ratios were not apparent until approximately 48 hours. Histological changes were evident within 12 hours, with a significant loss of neurons seen in the most severely damaged regions at 7 days. Diffusion-weighted imaging was the most sensitive technique for visualizing acute ischemic alterations. The water diffusion coefficient was the only magnetic resonance imaging parameter studied to indicate significant alterations within the first 4 hours after arterial occlusion in all five brain regions. CONCLUSIONS: The degree of change for a particular magnetic resonance imaging parameter appeared to be related to the location and extent of neuronal injury, with the most dramatic changes occurring within the areas displaying the most severe histological damage. These results indicate that complete specification of all brain regions affected by ischemic brain injury may require a combination of imaging strategies applied over a period of days and suggest the possibility of using magnetic resonance imaging to distinguish between permanent and reversible cell damage.

Animals↗

Temporal evolution and spatial distribution of the diffusion constant of water in rat brain after transient middle cerebral artery occlusion.

The regional distribution and temporal evolution of the diffusion coefficient (Dw) of water in rat brain was measured during and after transient middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 14) were subjected to 2 h of middle cerebral artery occlusion, induced by intracarotid insertion of a filament. Diffusion (n = 14) and perfusion (n = 7) weighted magnetic resonance imaging were performed before, and at various time points after MCA occlusion, ranging from 30 min up to 7 days. Our data demonstrate that the temporal profiles of Dw differ between the severely and the least damaged regions of tissue. In the core of the lesion, where the tissue evolved to necrosis, Dw declined significantly (P < 0.001) within 0.5 h after onset of ischemia, and remained depressed until 24 h after withdrawal of the suture. However, no statistically significant decline in Dw was found in the perifocal regions containing morphologically intact cells. Perfusion MRI qualitatively exhibited a hypoperfusion and reperfusion during, and after 2 h MCA occlusion, respectively. A significant (r > or = 0.71, P < 0.01) correlation was found between delta Dw (the difference in Dw between the ipsilateral ischemic and homologous contralateral control regions) obtained immediately before withdrawal of the suture (2 h of ischemia) and at specific early time points after withdrawal of the suture, and the degree of ischemic cell damage. No significant (P > 0.01) correlation was detected at an early time points of ischemia or at other time points after withdrawal of the suture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Histopathological correlations of nuclear magnetic resonance imaging parameters in experimental cerebral ischemia.

Changes in the nuclear magnetic resonance (NMR) parameters of spin-lattice relaxation (T1), spin-spin relaxation (T2), proton density (rho), and water diffusion (DNMR) were measured over time together with the histopathological status in three regions of rat brain cortex after permanent middle cerebral artery occlusion (MCA-O). Histological response ranged from severe irreversible damage (necrosis and cavitation) to relatively mild and apparently reversible damage. DNMR was the only NMR parameter which demonstrated a statistically significant change in all three regions of brain studied. Additionally, rho was significantly increased only in the region of brain studied which eventually progressed to necrosis and cavitation. Finally, data are presented which indicate that changes in T2, DNMR, and rho can occur independently of one another.

Animals↗

Acute elevation and recovery of intracellular [Mg2+] following human focal cerebral ischemia.

We used 31P magnetic resonance spectroscopy (MRS) to investigate changes in brain intracellular [Mg2+] following human focal cerebral ischemia. Mean brain pMg (where pMg = -log[Mg2+]) was significantly lower in the ischemic focus of all stroke patients (pMg = 3.34 +/- 0.28, n = 45, p < 0.01) when compared with normal controls (pMg = 3.50 +/- 0.08, n = 25). Ischemic brain pMg was also significantly reduced when the pH of the stroke region was acidotic (pH < 6.90, pMg = 3.07 +/- 0.44, n = 11, p < 0.01) and when the phosphocreatine index (PCrI = PCr/[PCr+Pi (inorganic phosphate)]) was reduced (PCrI < 0.47, pMg = 3.12 +/- 0.42, n = 13, p < 0.01). Mean brain pMg was significantly reduced at days 0 to 1 (acute) poststroke (pMg = 3.32 +/- 0.28, n = 26, p < 0.01) and at days 2 to 3 (subacute) poststroke (pMg = 3.38 +/- 0.28, n = 21, p = 0.03). There was also a significant (p < 0.01) correlation between decreased pMg and increased relative signal intensity of Pi (normalized by total phosphate signal, Pi/TP) for all stroke groups studied. During the temporal evolution of stroke, pH returned to normal levels by days 2 to 3, and pMg returned to normal by days 4 to 10 (subacute). PCrI and Pi/TP returned toward normal levels after 10 days (chronic), at a time when ischemic brain pH had become significantly alkalotic (pH = 7.10 +/- 0.24, n = 15, p < 0.01). Elevation of ischemic brain [Mg2+] is temporally linked to the acidotic phase of human stroke as well as the breakdown of energy metabolism. These acute changes in [Mg2+] may contribute to, or be a marker for, cellular injury.

Adenosine Triphosphate↗

Atraumatic quantitation of cerebral perfusion in cats by 19F magnetic resonance imaging.

We have noninvasively produced low-resolution, quantitative nuclear magnetic resonance images of cerebral blood flow in 2-ml voxels in eight cats. Typical signal-to-noise of 4 to 1 was obtained in cerebral voxels in 16.5-s epochs. Mean flow during normocapnia (paCO2 = 39 +/- 4 mm Hg) and hypercapnia (paCO2 = 62 +/- 4 mm Hg) was 53 +/- 20 ml/100 g-min and 140 +/- 36 ml/100 g-min, respectively. Fast flows in normocapnia were 94 +/- 13 and 182 +/- 39 ml/100 g-min in hypercapnia. These results suggest that an atraumatic quantitative imaging assessment of cerebral perfusion may be possible in humans using these techniques.

Animals↗

Human focal cerebral ischemia: evaluation of brain pH and energy metabolism with P-31 NMR spectroscopy.

The authors investigated early human focal ischemia with phosphorus-31 nuclear magnetic resonance spectroscopy at 1.89 T to characterize the temporal evolution and relationship of brain pH and phosphate energy metabolism. Data from 65 symptomatic patients were prospectively studied; none of the patients had had ischemic stroke in the internal carotid artery territory before. Twenty-eight neurologically normal individuals served as control subjects. Serial ischemic brain pH levels indicated a progression from early acidosis to subacute alkalosis. When acidosis was present there was a significant elevation in the relative signal intensity of inorganic phosphate (Pi) and significant reductions in signal intensities of alpha-adenosine triphosphate (ATP) and gamma-ATP compared with those of control subjects. Ischemic brain pH values directly correlated with the relative signal intensity of phosphocreatine (PCr) and the PCr index and inversely correlated with the signal intensity of Pi. There was a general lack of correlation between either ischemic brain pH or phosphate energy metabolism and the initial clinical stroke severity. The data suggest a link between high-energy phosphate metabolism and brain pH, especially during the period of ischemic brain acidosis, and the authors propose that effective acute stroke therapy should be instituted during this period.

Acidosis↗

Real-time flow measurements using echo-planar imaging.

The ultra-high-speed echo-planar imaging (EPI) method is combined with velocity encoding prior to EPI read-out, thereby allowing real-time measurement of flow. Results of EPI flow measurement experiments are presented on phantoms and human volunteers.

Blood Flow Velocity↗

Magnetization transfer contrast (MTC) in flash MR imaging.

Magnetization transfer between bound and free protons was used as a source of contrast in high speed MR imaging using the FLASH technique. Contrast in FLASH MR images was found to depend upon the reduced magnetization and the spin lattice relaxation rate of free protons in the presence of bound proton radio-frequency saturation. MTC FLASH imaging was thus used to estimate the variation with saturation frequency of free proton spin-lattice relaxation during magnetization transfer.

Animals↗

Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging.

The effects of cerebral ischemia in rat brain were monitored as a function of time using proton MR imaging. Spin-spin relaxation time (T2), proton density, and magnetization transfer contrast (MTC) were measured by MR imaging at various time intervals during a 1-week period following the induction of ischemic damage. Ischemic injury was characterized by a maximization of both T2 value and MTC appearance at 24 hr postischemic injury. These changes were accompanied by a gradual increase in MR observable water density over the first few days of ischemia. A reduction in the magnetization exchange rate between "free" and "bound" water protons as measured by MTC imaging is at least partially responsible for the elevation in T2 values observed during ischemia, and may accompany breakdown of cellular structure.

Animals↗

1H magnetic resonance imaging of normal brain tissue response to photodynamic therapy.

1H Magnetic resonance imaging (MRI) was used to study the effects of photodynamic therapy (PDT) on normal rat brain (n = 5) using T1-, T2-, diffusion-, and proton density (rho)-weighted images. Rats received intraperitoneal injections of 12.5 mg/kg of Photofrin II, and 48 hours later the dural area over the frontal cortex was treated with 35 J/cm2 of light (632 +/- 1 nm). The T1-, T2-, and diffusion-weighted images revealed an evolving high contrast region of brain that corresponded to the PDT-treated area. Lesioned brain exhibited significant increases in T1 and T2 relaxation times at 1 day (P less than 0.01) and 3 days (T1, P = 0.018; T2, P less than 0.01) after treatment, compared with the contralateral equivalent volume of nonlesioned brain. Water proton diffusion coefficient (DW) in the lesioned area decreased at 1 day (P = 0.026) and increased at 3 days (P = 0.012) compared with nonlesioned brain. An increase in the proton density ratio (rho D/rho O) from PDT (rho D) versus nonlesioned side (rho O) was found 3 days after PDT treatment (P = 0.03). The data indicate that the biophysical parameters obtained from magnetic resonance imaging scans, T1, T2, DW, and proton density, can be used to monitor changes in an evolving photochemically induced lesion.

Animals↗

Temporal evolution of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging.

We studied the effect of focal cerebral ischemia on the "state" of brain water using proton nuclear magnetic resonance imaging. Focal cerebral ischemia was induced in five halothane-anesthetized rats via tandem occlusion of the left common carotid artery and the left middle cerebral artery. The proton transverse relaxation time, the proton density, and the water diffusion coefficient were measured at various times from the same region of brain tissue from 1.5 to 168 hours after occlusion. Early measurements indicated significant changes in the transverse relaxation time (p = 0.004) and water diffusion coefficient (p = 0.002) of ischemic brain tissue compared with a homologous region from the contralateral hemisphere. However, the transverse relaxation time, proton density, and water diffusion coefficient in ischemic brain tissue showed different temporal evolutions over the study period. Diffusion coefficient weighting was superior to relaxation time and proton density weighting for the visualization of early cerebral ischemia. Our data suggest that nuclear magnetic resonance imaging is sensitive in detecting changes in proton-associated parameters during early cerebral ischemia and confirm significant changes (p less than or equal to 0.01) in the temporal evolution of transverse relaxation times, proton densities, and diffusion coefficients following middle cerebral artery occlusion.

Animals↗