Biomedical subjects

A J de Crespigny

Publications and source records attributed to A J de Crespigny.

At least 19 recordsLinked to original sources

PubMed2005

A comparison of CH3-DTPA-GD (NMS60) and GD-DTPA for evaluation of acute myocardial ischemia.

PURPOSE: Our objective was to evaluate the use of a new medium weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd-complex containing three Gd(3+) atoms, molecular weight 2158 Da) compared to gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in a pig myocardial ischemia model. MATERIALS: We used 13 male white hybrid pigs. Animals were scanned in the acute phase 2-3 h after the onset of myocardial ischemia. Scans were acquired on a 1.5T GE Signa with dynamic T1-weighted imaging during a bolus injection of 0.1 mmol(gd)/kg of either NMS60 or Gd-DTPA, 2D CINE at 5 min after injection, and T1-weighted spin-echo imaging up to 60 min. RESULTS: The postcontrast CINE scans showed improved contrast-to-noise ratio after NMS60 injection, compared to Gd-DTPA. There was significantly greater enhancement with NMS60 in both normal myocardium and in the ischemic lesion on T1-weighted spin-echo scans up to 60 min after injection. The dose ranging study shows a 24% greater enhancement with NMS60 compared to Gd-DTPA. DISCUSSION: This new medium weighted contrast agent offers improved enhancement for cardiac MRI, compared to Gd-DTPA, with similar washout kinetics and lower toxicity, and may prove useful for better detection of myocardial ischemia as well as delayed or hyperenhancement after reperfusion.

Acute Disease↗

PubMed2004

A comparative evaluation of CH3-DTPA-Gd (NMS60) for contrast-enhanced magnetic resonance angiography.

In a canine model the signal dynamics of a new oligomer-based MR contrast agent (NMS60, 2158 Da) were compared to Gd-DTPA to investigate the agents' potential for magnetic resonance angiography (MRA). Twelve male mongrel dogs were imaged sequentially under anesthesia with two different MRA sequences (Tlw 3DSPGR). Initial enhancement was measured every 9 s for eight points in time. Thereafter, spatial highly resolved MRAs were obtained at 5, 10, 15, 20, 30, 45, and 60 min post-injection of two different dosages. Over the first 20 s following bolus administration the average arterial enhancement of 0.1 mmol(Gd)kg NMS60 was 44% greater than Gd-DTPA. Twenty minutes post-injection the relative signal intensity of NMS60 was as high as the peak signal intensity with Gd-DTPA at the same dosage level (0.1 mmol(Gd)/kg). In the animals that received NMS60 injections the vascular conspicuity was overly superior to those who received Gd-DTPA. No significant toxicity effects were noted for either dosage level. The intermediate weight contrast agent NMS60 offers greater vascular enhancement and retention time than Gd-DTPA. For a given set of optimized imaging parameters this offers improved spatial details, less arterial/venous overlap, and better vascular contrast.

Animals↗

PubMed2001

Comparison of diffusion, blood oxygenation, and blood volume changes during global ischemia in rats.

Rapid diffusion, blood oxygenation, and blood volume weighted echo planar imaging was used to monitor global cerebral ischemia by cardiac arrest in rats. Serial CBV measurements used intravascular iron oxide contrast media (iron dextran). ADC dropped by 5% within 20 sec of cardiac arrest, then continued to decay slowly until a larger rapid drop after 2 min. After iron oxide injection, the initial 5% drop was not observed. The transverse relaxation rate (R(2), R(*)(2) no iron injection) increased rapidly after cardiac arrest, peaking at about 30 sec, then declining towards baseline. The CBV dropped by about 50% within 20 sec. The initial 5% ADC drop may be a vascular artifact. The rapidity of the CBV-weighted signal drop suggests a flow-mediated contribution to the iron oxide contrast mechanism. Magn Reson Med 45:10-16, 2001.

Animals↗

PubMed2001

Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke.

BACKGROUND AND PURPOSE: Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age. METHODS: Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke. The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)). RESULTS: The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter. The lesion ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old. All signal intensities remained high throughout follow-up. SI(DWI) showed no significant change during the first week but decreased thereafter. SI(T2) initially increased, decreased slightly during week 2, and again increased after 14 days. SI(FLAIR) showed the same initial increase as the SI(T2) but remained relatively stable thereafter. CONCLUSION: Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age. Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values.

Aged↗

PubMed2000

MRI of focal cerebral ischemia using (17)O-labeled water.

This work presents a novel approach for quantifying low concentrations of H(2)(17)O in vivo and explores its utility for assessing cerebral ischemia. Oxygen-17 enriched water acts as a T(2) shortening contrast agent whose effect can be suppressed by decoupling at the (17)O frequency during TE interval in a spin-echo MR image. Serial T(2)-weighted echo planar images were acquired in phantoms and rat brain with decoupler power alternated every eight images. The resulting periodic signal change (proportional to H(2)(17)O concentration) was detected by cross-correlating the square-wave decoupler power timecourse with the signal intensity in each voxel. Natural abundance (0.037 atom%) images of H(2)(17)O in rat brain were generated. The transverse relaxivity of H(2)(17)O in brain was estimated, R(2) = 2.4+/-0.5 s(-1)(atom%)(-1). After bolus injection of 1 ml of 10 atom% H(2)(17)O, brain H(2)(17)O concentration was estimated at 0.06+/-0.01 atom%. In the rat focal ischemia model, (17)O cross-correlation maps compared well with diffusion and Gd-DTPA perfusion images to indicate infarct location. Magn Reson Med 43:876-883, 2000.

Animals↗

PubMed1999

High-resolution mapping of discrete representational areas in rat somatosensory cortex using blood volume-dependent functional MRI.

The present study documents the use of an iron oxide-based blood-pool contrast agent in functional magnetic resonance imaging to monitor activity-related changes in cerebral blood volume (CBV) resulting from peripheral sensory stimulation and the application of this technique to generate high-resolution functional maps. Rats, anesthetized with alpha-chloralose, were imaged during electrical stimulation (3 ms, 3 Hz, 3 V) of forelimb or hindlimb. Activation maps were generated by cross-correlation of the measured signal response and a square-wave function representative of the stimulus for each image pixel. Multislice imaging produced functional maps consistent with the known functional anatomy of rat primary somatosensory (S-I) cortex. Imaging with improved temporal resolution demonstrated rapid (<6 s) CBV increases which were sustained and relatively stable (coefficient of variation = 0.17 +/- 0.02) for forelimb stimulation periods of up to 5 min. Enabled by this sustained response we generated high-resolution (approximately 100 micrometer in-plane) functional maps showing discrete forelimb and hindlimb activation. This technique offers many advantages over other methods for the study of brain activity in the rat and has resolution sufficient to be useful in reorganization studies.

Animals↗

PubMed1999

Dynamic contrast-enhanced MRI of Implanted VX2 tumors in rabbit muscle: comparison of Gd-DTPA and NMS60.

We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.

Animals↗

PubMed1999

Rapid monitoring of diffusion, DC potential, and blood oxygenation changes during global ischemia. Effects of hypoglycemia, hyperglycemia, and TTX.

BACKGROUND AND PURPOSE: The increasing interest in diffusion-weighted MRI (MRI) for diagnosis and monitoring of acute stroke in humans calls for a sound understanding of the underlying mechanisms of this image contrast in acute cerebral ischemia. The present study aimed to show that a rapid decrease in brain-water apparent diffusion coefficient (ADC) occurs coincident with anoxic depolarization and that this change is delayed by hyperglycemia and sodium channel blockade but accelerated by hypoglycemia. METHODS: Rats were divided into groups: normoglycemic, hypoglycemic, and hyperglycemic, and those given local tetrodotoxin (TTX) application. Cardiac arrest was effected by intravenous KCl injection during serial high-speed diffusion and blood oxygenation-sensitive gradient-recalled echo MRI. Brain DC potential was recorded simultaneously. Serial ADC maps were calculated from the diffusion-weighted data and fitted to a model function to measure the delay between cardiac arrest and rapid ADC decrease. RESULTS: The time of anoxic depolarization indicated by DC change agreed well with the rapid drop in ADC in all groups; both were accelerated with hypoglycemia and delayed by hyperglycemia. A more gradual ADC decline occurred before anoxic depolarization, which was more pronounced in hyperglycemic animals and less pronounced in hypoglycemic animals. Rapid drop in ADC was also delayed by local TTX application. Changes in gradient-recalled echo image intensity were not significantly different among groups. CONCLUSIONS: While much of the ADC decrease in ischemia occurs during anoxic depolarization, significant but gradual ADC changes occur earlier that may not be due to a massive loss in ion homeostasis.

Animals↗

PubMed1998

High-resolution functional magnetic resonance imaging of the rat brain: mapping changes in cerebral blood volume using iron oxide contrast media.

Contrast-enhanced magnetic resonance imaging was used to produce high-resolution activation maps reflecting local changes in cerebral blood volume after a simple sensory stimulus. Activation of the forelimb region of the somatosensory cortex was performed in alpha-chloralose-anaesthetized rats with an electrical stimulus (5 V, 3 Hz) delivered through needle electrodes placed subcutaneously on the left forelimb. A gradient echo magnetic resonance imaging sequence, sensitive to changes in the relative amount of deoxyhemoglobin within the cerebral vasculature, produced a 4.05%+/-1.69% increase in signal intensity. This effect was enhanced with an injection of an intravascular iron oxide contrast agent (Combidex, Advanced Magnetics), resulting in a 9.11%+/-1.52% decrease in signal intensity.

Animals↗

PubMed1996

MR detection of cortical spreading depression immediately after focal ischemia in the rat.

The suture model for middle cerebral artery occlusion (MCAO) was used to induce acute ischemia in rats remotely within a magnetic resonance (MRI) scanner. Serial MR diffusion weighted imaging (DWI) was performed during remote MCAO using an echo planar imaging technique. MR perfusion imaging was performed before and after occlusion using the bolus tracking technique. Transient apparent diffusion coefficient (ADC) changes were detected in six of seven rats as early as 2.7 +/- 1.5 min post MCAO. ADC values declined transiently to 70.1 +/- 6.0% of control and recovered to 95.5 +/- 6.8% of control within 3.3 +/- 2.9 min. These ADC changes propagated bidirectionally away from the ischemic core with a speed of 3.0 +/- 1.1 mm/min. Transient ADC decreases only occurred in ischemic areas characterized by moderately decreased tissue perfusion. Propagation toward cortical regions with severe tissue perfusion deficits was not detected. DWI can detect the earliest dynamic, reversible ADC changes in the ischemic tissue. The speed of propagation of the decreasing ADC wave, the waveform characteristics, and the occurrence in moderately perturbated tissue are compatible with cortical spreading depression.

Animals↗

PubMed1996

Experimental cerebral venous thrombosis: evaluation using magnetic resonance imaging.

Diffusion-weighted (DWI), dynamic contrast-enhanced (perfusion imaging), and conventional spin-echo magnetic resonance imaging (MRI) were applied to characterize the pathophysiology of cerebral venous thrombosis (CVT) in the rat. We induced CVT by rostral and caudal ligation of the superior sagittal sinus (SSS) and injection of a thrombogenic cephalin suspension. The resulting pathology was monitored in an acute and long-term study group. Evans blue and hematoxylin-eosin staining was performed for comparison with MRI data. A subgroup of animals was treated with i.v. tissue plasminogen activator (t-PA). Successful thrombosis of the SSS was confirmed by macropathology or histopathology in all rats. Parenchymal lesions as shown by MRI, however, were present only in animals with additional involvement of cortical cerebral veins (11 of 18 rats). The early pathology was clearly detected with the DWI. The apparent diffusion coefficient declined to 56 +/- 7% of control value at 0.5 h and slowly increased to 84 +/- 8% by 48 h. Perfusion imaging showed parasagittal perfusion deficits. Treatment with t-PA partially resolved the hyperintensity on DWI. Evidence of blood-brain-barrier disruption was observed 2 to 3 h after induction of CVT. In conclusion, experimental CVT is characterized by early cytotoxic edema closely followed by vasogenic edema. The t-PA treatment partially reversed the DWI signal changes consistent with regional tissue recovery, as shown by histopathology. These results encourage the use of cytoprotective drugs in addition to anticoagulant or thrombolytic therapy.

Animals↗

PubMed1996

Recovery of apparent diffusion coefficient after ischemia-induced spreading depression relates to cerebral perfusion gradient.

BACKGROUND AND PURPOSE: Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression. DWI and dynamic contrast-enhanced MRI were applied to study the characteristics of spreading depression and the correlation between ADC recovery time and tissue perfusion in focal ischemia. METHODS: Serial DWI was performed during remote middle cerebral artery occlusion in rats (n = 5) with an echo-planar imaging technique. ADC maps were calculated and ADC values displayed as a function of time in user-defined regions of interest with a time resolution of 12 to 16 seconds. Dynamic contrast-enhanced MRI was performed for qualitative correlation of ADC changes with tissue perfusion. RESULTS: Recovery time of transient ADC decreases correlated with the degree of the perfusion deficit (r = .81, P < .001). Slowly recovering ADC declines were found close to the ischemic core and correlated with severe perfusion deficit, while short-lasting ADC declines were typically found in moderately malperfused or normal tissue. Transient ADC decreases originated in the subcortical and cortical ischemic border zones and propagated along the cortex with a velocity of 2.9 +/- 0.9 mm/min. CONCLUSIONS: The variation in the recovery time of transient ADC decreases in the ischemic periphery reflects the gradient of the tissue perfusion. Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra.

Animals↗

PubMed1995

Navigated diffusion imaging of normal and ischemic human brain.

The principal barrier to clinical application of diffusion-weighted MR imaging is the severe image degradation caused by patient motion. One way to compensate for motion effects is the use of a "navigator echo" phase correction scheme. In this work, a modification of this technique is introduced, in which the phase correction step is performed in the frequency domain (i.e., after the readout Fourier transform). This significantly improves the robustness of the navigator echo approach and, when combined with cardiac gating, allows diagnostic quality diffusion-weighted images of the brain to be routinely obtained on standard clinical scanner hardware. The technique was evaluated in phantom studies and in 23 humans (3 normal volunteers and 20 patients). Diffusion anisotropy and apparent diffusion coefficient maps were generated from the image data and showed decreased apparent diffusion in acute stroke lesions and, in several cases, increased apparent diffusion in chronic stroke lesions.

Aged↗

PubMed1993

Improved sensitivity to magnetic susceptibility contrast.

Changes in the local magnetic susceptibility of brain tissue due to injected paramagnetic contrast agent are manifest as both a line-broadening and frequency shift of the water resonance. By combining these two effects, the sensitivity of gradient recalled echo images to such changes can be increased.

Animals↗

PubMed1993

Early detection of regional cerebral ischemia using high-speed MRI.

BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging (MRI) has been shown to be effective in detailing regions of cerebral ischemia in which water proton translations or motions have been slowed. The corresponding perfusion patterns, however, have not been correlated. Further, the hemodynamics of normal and ischemic tissues and the changes due to mild insults are also not clear. This study describes high-speed MRI techniques and observations found in the early detection of regional cerebral ischemia in the cat. METHODS: Gradient-echo and spin-echo-planar MRI was used with middle cerebral artery balloon occluders to induce transient ischemia and reperfusion. RESULTS: Apparent diffusion fell within minutes after middle cerebral artery occlusion and correlated with near-total or total perfusion deficits. Reactive hyperemia, apnea, and vasodilatation appeared to be changed in ischemic and normal brain. CONCLUSIONS: Characterization of early ischemic events is dramatically improved when the motions of water (apparent diffusion), delivery of water (perfusion), and response to hemodynamic perturbations (regulatory response) are measured. All can be accomplished with high-speed MRI techniques described herein.

Animals↗

PubMed1991

Cardiac tagging in the rat using a DANTE sequence.

We demonstrate the application of a DANTE tagging sequence to in vivo imaging of the rat heart. This sequence generates narrow parallel tag lines in a short space of time and is combined with cardiac gating to image the heart wall at eight points throughout the cycle.

Animals↗

PubMedDate not supplied

Rapid MR imaging of a vascular challenge to focal ischemia in cat brain.

Deoxygenated blood was effectively used as a magnetic resonance (MR) susceptibility contrast agent to distinguish perfused and nonperfused (ischemic) regions in a focal ischemia model in cat brain at 2T. Modulation of cerebral blood oxygenation levels in response to apnea was followed in real time with T2*-weighted (gradient-recalled) echo-planar MR imaging. Signal loss in the T2*-weighted images occurred only in perfused tissues as blood became globally deoxygenated. These data complemented information from diffusion-weighted and contrast agent bolus-tracking images. In addition, observation of the signal recovery behavior on reventilation in both normal and ischemic brain offered potentially useful information about the state of the cerebral autoregulatory mechanism.

Animals↗

PubMedDate not supplied

MR imaging of blood oxygenation-dependent changes in focal renal ischemia and transplanted liver tumor in rat.

The potential of using fast magnetic resonance (MR) imaging in conjunction with apnea-induced blood deoxygenation for the noninvasive monitoring of relative perfusion in the rat abdomen has been studied with two experimental models: glycerol-induced focal renal ischemia and transplanted liver tumor. Gradient-echo echo-planar imaging (GRE-EPI) (TE of 20 msec at 2T) of liver and kidney was performed before, during, and after a 60-second apnea episode and then was followed in the same rat by contrast-enhanced (a) GRE-EPI and (b) T1-weighted spin-echo imaging (TR msec/TE msec = 200/6) with polylysine-(gadolinium-DTPA [diethylenetriaminepentaacetic acid]). The results indicate that a noninvasive vascular challenge due to apnea can be used for the detection of focal tissue perfusion abnormalities in rat kidney and liver tumor.

Animals↗