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Biomedical subjects

J E Kirsch

Publications and source records attributed to J E Kirsch.

At least 19 recordsLinked to original sources

Cortical activation in confrontation naming.

Functional magnetic resonance imaging was used to detect cortical activation in the right and left perisylvian cortex of seven young adult right-handed volunteers in response to a letter fluency task and to a visual naming task using standardized line drawings. Both letter fluency and visual naming activated left dorsolateral prefrontal cortex (Brodmann's areas 6, 9, 44 and 45). Only visual naming activated area 37 (a cortical region with strong connections to visual association areas), visual association area 19, and areas 39 and 21 previously shown to activate with auditory semantic tasks. This study supports a role for area 37 as participant in a visual lexicosemantic processing network which may otherwise overlap the auditorysemantic network.

Adult↗

Analysis of noise in phase contrast MR imaging.

In this work we analyze the effects of inherent random noise on the detectability of low-contrast vessel structures that possess slow flow. When flow is encoded in more than one direction, the number of independent noise contributions increases in addition to the scan time. In a fast-flow scenario, only the noise contribution from sampling along the direction of flow is of any significance. At slow flow rates, however, it becomes necessary to account for the noise in each encoded Cartesian direction. The degree to which noise affects low-contrast detectability also depends on the method of phase contrast image processing employed. A theoretical analysis of the statistical properties of signal and noise in processed phase contrast magnitude images is presented and verified from experimental MR image data. Results show a progressively increased bias in the processed phase contrast image magnitude at slow flow rates due to contributions from inherent random noise. The amount of this bias increases with the number of physical directions in which flow is encoded and is larger for complex difference processed images than for phase difference processing. Correspondingly, the output signal-to-noise ratio associated with flow is compromised.

Biometry↗

Frontal lobe phosphorus metabolism and neuropsychological function in aging and in Alzheimer's disease.

31P Magnetic resonance spectroscopy of the frontal lobe was performed in 17 patients with Alzheimer's disease (AD), 8 elderly controls (EC), and 17 young controls (YC). The phosphocreatine/inorganic phosphate (PCr/Pi) ratio in AD (2.32 +/- 0.26 SD) was significantly lower than in EC (2.65 +/- 0.41). In AD patients, a correlation was observed between the PCr/Pi ratio and the dementia rating scale (r = -0.50, p = 0.04). A significant positive correlation between PCr/Pi ratio and age was observed in both AD (r = 0.67, p = 0.003) and YC (r = 0.63, p = 0.006) groups, however, suggesting caution in interpretation of this ratio in AD. We did not find differences between AD, EC, or YC in any other spectroscopic measure. A significant sex difference in the phosphomonoester/phosphodiester ratio (PME/PDE) ratio was observed in AD brain. Females had a lower PME/PDE ratio than males.

Adult↗

Magnetization transfer and high-dose contrast in early brain infection on magnetic resonance.

RATIONALE AND OBJECTIVES: The authors studied the effect of contrast dose, use of magnetization transfer (MT), and temporal delay on the visualization of contrast enhancement with gadoteridol (Gd HP-DO3A) in a canine brain abscess model. METHODS: Alpha streptococcus brain abscesses were studied in five dogs at 1.5 tesla (T) 1 and 5 days after implantation. Scans were performed 1, 11, and 21 minutes after contrast was administered, using an initial dose of 0.1 mmol/kg. A supplemental contrast injection of 0.2 mmol/kg was given (for a cumulative dose of 0.3 mmol/kg), with scans repeated at 31, 41, and 51 minutes. RESULTS: Lesion conspicuity on day 1 was greater at high-contrast doses (0.3 mmol/kg) compared with standard doses (0.1 mmol/kg), regardless of whether imaging was performed without (0.89 +/- 0.02 compared with 0.26 +/- 0.08) or with (0.97 +/- 0.04 compared with 0.28 +/- 0.06) MT. High-dose, MT, and a delay after contrast was injected all produced a statistically significant improvement. On blinded review of films obtained 11 and 14 minutes after injection, enhancement of the lesion could not be identified with certainty in two of five dogs at a dose of 0.1 mmol/kg, regardless of whether MT was used. Enhancement was seen consistently in all lesions at 0.3 mmol/kg. On day 5, results were comparable, with greater absolute enhancement. CONCLUSIONS: In early brain infection, high-contrast doses (0.3 mmol/kg), MT, and a moderate delay after injection all improve visualization of lesion enhancement.

Animals↗

Visualization of blood-brain barrier disruption on MR images of cats with acute cerebral infarction: value of administering a high dose of contrast material.

OBJECTIVE: The detection of blood-brain barrier disruption in patients with cerebral infarction by means of contrast-enhanced MR images improves the specificity of diagnosis, enables lesion dating, and on occasion improves lesion detection. Accordingly, we performed a study to determine the extent of visualization of disruption of the blood-brain barrier on contrast-enhanced MR images, with specific attention to contrast dose, in a cat model of acute cerebral infarction. We used doses of 0.1 and 0.3 mmol/kg of a gadolinium chelate, gadoteridol, which is characterized by extracellular distribution and renal excretion, and was approved by the Food and Drug Administration for clinical use at these doses. MATERIALS AND METHODS: Blood flow in the middle cerebral artery was occluded unilaterally in seven cats for 1 hr, followed by 4 hr of reperfusion. T2- and T1-weighted MR images were obtained before the injection of contrast material. After injection, the time course of enhancement was observed for 1 hr by repeated sequential acquisition of T1-weighted images. Five cats received an initial injection of 0.1 mmol/kg of contrast material, supplemented 33 min later by 0.2 mmol/kg (cumulative dose, 0.3 mmol/kg). Two cats received a single injection of contrast material, either 0.1 or 0.3 mmol/kg. The images were reviewed in a prospective fashion by a single observer, who was blinded to the dose of contrast material and the timing of image acquisition, in order to detect abnormal contrast enhancement. Changes in single intensity were quantified by region-of-interest measurements. RESULTS: Enhancement at 4 and 13 min, respectively, after injection of contrast material was 25 +/- 10% and 38 +/- 7% with 0.1 mmol/kg, vs 80 +/- 12% and 100 +/- 15% with 0.3 mmol/kg (n = 5). The difference between doses was statistically significant (p < .002) for all time points. Abnormal contrast enhancement was visible in three of six cats that received 0.1 mmol/kg and in all cats that received 0.3 mmol/kg. By 13 min after injection, enhancement had peaked with a dose of 0.1 mmol/kg and was within 20% of maximum with a dose of 0.3 mmol/kg. CONCLUSION: Detection of disruption of the blood-brain barrier in acute cerebral infarction in cats is improved when high doses (0.3 mmol/kg) of contrast material are used. Disruption may not be visualized when 0.1 mmol/kg, the currently accepted standard dose, is used.

Animals↗

Magnetic resonance contrast agents in neuroimaging. New agents and applications.

Of the four gadolinium chelates in clinical use worldwide, only three are available in the United States: gadoteridol, gadodiamide, and gadopentetate dimeglumine. Although gadopentetate dimeglumine is still administered in many clinical practices, a consequence of being the first agent developed (1988) and until recently the only agent available, gadoteridol demonstrates a higher index of safety--at least on theoretical grounds. With linear chelates such as gadopentetate dimeglumine and gadodiamide, greater release of free gadolinium ion occurs in vivo owing to lower thermodynamic and kinetic stability. The concern with respect to demetallation and resultant increased chronic deposition of gadolinium ion in marrow and liver is greater with gadodiamide. Drug safety appears not to be an issue at high dose for gadoteridol, the only agent approved in this regards. The safety of the other chelates at high dose has yet to be established. The nonionic character of the two newer agents (gadoteridol and gadodiamide) is not of great importance in current clinical practice, in which most examinations are still performed with a dose of 0.1 mmol/kg given as a slow infusion. The non-ionic nature of the newer MR contrast agents may become clinically important in the future, with more common application of bolus injection and high dose. High contrast dose (0.3 mmol/kg) is advocated in routine MR clinical practice for the evaluation of intracranial metastatic disease. Only with prior evidence for multiple metastases and in patients for whom the detection of additional lesions would not influence therapy can the use of standard dose (0.1 mmol/kg) be justified.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

Assessment of cerebral perfusion by first-pass, dynamic, contrast-enhanced, steady-state free-precession MR imaging: an animal study.

OBJECTIVE: The purpose of this study was to determine whether cerebral perfusion could be assessed with a conventional 1.5-T MR imaging system by applying a steady-state free-precession (SSFP) technique during bolus IV injection of contrast material (gadoteridol). Normal and abnormal perfusion states and the effect of the dose of contrast material were studied in cats. MATERIALS AND METHODS: Nine healthy anesthetized cats were imaged after administration of 0.5 mmol/kg (n = 5), 0.25 mmol/kg (n = 2), and 0.1 mmol/kg (n = 2) of gadoteridol. Six cats with an acute infarct of the middle cerebral artery (five cats 10 min after and one cat 1 hr after vessel occlusion) were evaluated at a dose of 0.5 mmol/kg. The middle cerebral artery was ligated in each instance by use of a snare placed around the vessel during surgery, which was performed via a transorbital approach. Each animal was imaged with spin-echo T2-weighted (3000/45,90 [TR/TE]) and T1-weighted (500/10) techniques before contrast material was injected. SSFP images (12/18, 80 degrees tip angle) were acquired sequentially (each with a 1-sec acquisition time and no interimage delay) immediately before and for 45 sec after IV injection of a bolus of gadoteridol. RESULTS: The first-pass effect in both normal gray and white matter was dose dependent, with a greater magnitude of change seen at higher doses of contrast material. A 55% decrease in signal intensity of normal peripheral gray matter was observed during the first pass after bolus injection of 0.5 mmol/kg gadoteridol, compared with a 23% decrease and a 17% decrease at doses of 0.25 and 0.1 mmol/kg, respectively. High temporal (one image per second) and spatial (1.5 x 1.5 x 6.0 mm) resolution was achieved, with sufficient sensitivity that both visual and statistical differentiation of normal and abnormal gray and white matter was possible. Ten minutes after vessel occlusion, the change in signal intensity during the first pass was 45 +/- 5% and 27 +/- 9% for normal central gray and white matter, respectively, as compared with 20 +/- 2% and 11 +/- 5% for ischemic central gray and white matter, respectively. CONCLUSION: Cerebral perfusion can be assessed on conventional 1.5-T MR imaging systems by combining high-dose IV bolus injection of contrast material (in this instance, using gadoteridol) with dynamic SSFP imaging.

Animals↗

Enhanced liver MR: contrast agents and imaging strategy.

Contrast enhancement in liver MR can be achieved by a variety of fundamentally different strategies. The published clinical literature regarding Gd DTPA (gadopentetate dimeglumine), Gd HP-DO3A (gadoteridol), Gd BOPTA (gadobenate dimeglumine), Mn DPDP, and AMI-25 is reviewed, followed by a brief discussion of two new iron particulate agents currently in preclinical trials. Different imaging techniques also must be used for visualization of contrast enhancement depending on the specific type of agent utilized. With both gadolinium and manganese chelates, T1 weighted sequences are used to visualize the effect of the contrast agent. There is positive enhancement (an increase in signal intensity) of normal liver parenchyma post-contrast due to enhanced T1 relaxation. With iron particulate agents, T2 weighted sequences are used. In this instance, there is negative enhancement (a decrease in signal intensity) of normal liver post-contrast due to enhanced T2 relaxation. Clinical use at present is limited to the extracellular gadolinium chelates, with bolus injection and dynamic imaging improving efficacy. Current research also supports the use of a high dose (0.3 mmol/kg) for improved lesion detectability, a finding now clinically relevant due to the recent approval of Gd HP-DO3A at both standard and high doses.

Contrast Media↗

High-dose applications of gadolinium chelates in magnetic resonance imaging.

Administration of gadolinium chelates at doses greater than 0.1 mmol/kg IV can potentially improve both lesion detection and the assessment of tissue perfusion. Preliminary results are presented in clinical patients and two animal models. In human intracranial metastatic disease, administration of 0.3 (cumulative dose) mmol/kg gadoteridol (Gd HP-DO3A) has permitted detection of additional lesions not visualized at 0.1 mmol/kg. In a rabbit model of focal liver disease, 0.5 mmol/kg IV provided superior enhancement of both normal parenchyma and lesion rim compared to doses of 0.25 and 0.1. Dynamic imaging (T1-weighted turbo-FLASH) immediately following bolus injection of 0.5 mmol/kg permitted direct visualization (on unsubtracted images) of an acute perfusion defect in the cat brain not visible on conventional T1- and T2-weighted scans.

Animals↗

Basic principles of magnetic resonance contrast agents.

The use of contrast agents in MRI is well established as a means to improve diagnosis. MRI differs from other imaging modalities because signal and contrast are multiparametric in both the properties of the tissue and the method of measurement. Contrast depends on differences in proton-spin density, magnetic susceptibility, molecular diffusion and perfusion, and T1 and T2 relaxation times. Relaxivity contrast agents, those that focus on shortening relaxation times, are most commonly employed in the form of paramagnetic chelates and depend on a variety of mechanisms, including concentration, number of ion-coordination sites, spin quantum number, magnetic moment, ion-to-proton distance, and correlation time constants characteristic of the chemical and molecular structure. A sound understanding of the principles of general contrast mechanisms, contrast agent design, and MRI techniques used in conjunction with contrast agents is vital to ensure proper enhancement and optimal diagnostic results.

Contrast Media↗

Clinical comparison of three-dimensional MP-RAGE and FLASH techniques for MR imaging of the head.

Three-dimensional (3D) MP-RAGE (magnetization-prepared rapid gradient-echo) imaging was evaluated as a high-resolution 3D T1-weighted brain imaging technique for patients with suspected neurologic disease. Fourteen patients were studied. In five, 3D MP-RAGE images were compared with 3D FLASH (fast low-angle shot) images. Signal difference--to-noise ratios and T1 contrast were not statistically different for 3D MP-RAGE images as opposed to 3D FLASH images. Advantages intrinsic to the application of 3D MP-RAGE sequences include decreased imaging time and decreased motion artifact. With this technique, it is possible to perform a relatively motion-insensitive, T1-weighted screening brain study with voxel resolution of 1.0 x 1.4 x 2.0 mm or smaller, in an imaging time of 5.9 minutes or less--permitting offline (poststudy) reconstruction of high-resolution images in any desired plane.

Brain↗

High-dose gadoteridol in MR imaging of intracranial neoplasms.

Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease.

Adult↗

Contrast-enhanced MR angiography.

Magnetic resonance (MR) angiography, although still in its infancy, is recognized as a valuable diagnostic tool. Investigation of the utility of contrast media as applied to MR angiography is, to no surprise, preliminary. In restricted instances, with present techniques, contrast media-enhanced MR angiography can provide additional valuable diagnostic information. Inspection of two-dimensional images (as opposed to three-dimensional projections) and comparison of MR images before and after administration of contrast agent are particularly important. Improved visualization of intracranial aneurysms, arteriovenous malformations, venous anomalies, and arterial occlusions has been demonstrated on three-dimensional time-of-flight MR angiograms after intravenous administration of a gadolinium chelate, relative to studies performed before administration of the contrast agent.

Animals↗

Gadoteridol dose dependence in MR imaging of a liver abscess model.

A necrotic liver abscess model was studied with magnetic resonance (MR) imaging at 1.5 T before and after intravenous administration of gadoteridol at doses of 0.1, 0.25, and 0.5 mmol/kg in 24 rabbits. Enhancement characteristics and lesion delineation were assessed with both breath-hold and non-breath-hold imaging techniques. Lesion delineation, as assessed both by signal intensity measurements and evaluations by two image readers blinded to imaging technique, was greatest on high-dose (0.5 mmol/kg) breath-hold images. Lesion rim enhancement was seen consistently only on postcontrast images obtained at a dose of 0.5 mmol/kg and progressed with time after injection of contrast material.

Animals↗

Repeat cerebral blood volume assessment with first-pass MR imaging.

The feasibility of performing multiple first-pass studies with dynamic, contrast material-enhanced magnetic resonance (MR) imaging was evaluated in a cat model of acute middle cerebral artery (MCA) ischemia. Two dynamic series of SSFP (steady-state free precession) images were acquired in each animal (n = 5) with a conventional 1.5-T imager. The initial first-pass study was acquired at 60 minutes after MCA occlusion, and the second study at 70 minutes, with each performed during an intravenous bolus injection of a 0.5 mmol/kg dose of gadoteridol. In both first-pass studies, differentiation of normal and ischemic gray and white matter was highly statistically significant. At a threshold of P < .01, no statistically significant difference in the peak signal intensity between the first and second studies was noted. A difference between the two studies in the recovery to baseline was seen, presumably due to T1 effects. First-pass MR studies can be repeated within the time frame of a single clinical examination, expanding their utility.

Animals↗

Cerebral infarction: assessment of patterns using ultra-fast MR contrast imaging.

We describe a rapid MR imaging technique, applying functional analysis to images obtained during the tissue transit of injected contrast material into the cerebral circulation, which has potential for assessment of the altered hemodynamics in cerebral ischemia. This technique utilized turbo-FLASH imaging maximizing the T1 relaxivity properties of gadopentetate dimeglumine with positive contrast enhancement.

Cerebral Infarction↗

Cerebral hemodynamics and cerebral blood volume: MR assessment using gadolinium contrast agents and T1-weighted Turbo-FLASH imaging.

PURPOSE: To assess the degree and regional pattern of first-pass brain enhancement using dynamic MR imaging. MATERIALS AND METHODS: Ultrafast MR imaging (1.06-second acquisition time per image) was performed in 19 healthy subjects following a bolus IV injection of a gadolinium contrast agent; 36 patients with suspected pathology were studied using the same protocol. RESULTS: Calculated percent blood volumes were 4.9% for right cortical gray matter, 4.8% for left cortical gray matter, and 2.6% for white matter. Subtraction images were obtained that depicted the first pass "blood pool" pattern of enhancement (gray and white matter) which was significant. CONCLUSION: Preliminary evidence suggests utility for cerebral "blood pool" imaging, especially if reduced image acquisition times can be achieved.

Adult↗