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Biomedical subjects

R C Brasch

Publications and source records attributed to R C Brasch.

At least 37 records · Page 2Linked to original sources
PubMed1999

MR imaging of the arthritic rabbit knee joint using albumin-(Gd-DTPA)30 with correlation to histopathology.

The purpose of this study was to demonstrate a technique, in a pilot study, for measuring abnormal capillary permeability in synovial tissue of rabbit arthritic knees using dynamic MRI with a gadolinium-based blood pool agent. Arthritis, simulating rheumatoid arthritis, was induced in knees of 8 rabbits by intra-articular injection of carrageenan (n = 4) or ovalbumin (n = 4). Sequential fat presaturated T1-weighted Spoiled Grass images were obtained before and up to 30 min after intravenous administration of albumin-(Gd-DTPA)30. Estimates of synovial tissue plasma-volume (PV), fractional-leak-rate (FLR), and permeability-surface-area-product (PS) were computed. Histologic correlation was obtained in the corresponding regions. Dynamic MRI showed extravasation of albumin-(Gd-DTPA)30 into hypertrophic synovium in six of the eight arthritic knees. Histologic examination of these six knees showed markedly inflamed synovium. The two knees that did not show abnormal vascular permeability contained non-hypertrophic synovium. None of the rabbits showed abnormal permeability in muscle. MRI derived microvascular characteristics (PV, FLR and PS) correlated positively (r2 = 0.51, 0.97 and 0.86) with the histology. Factors involving the structural and functional microvascular characteristics of synovial tissue can be estimated non-invasively using albumin-(Gd-DTPA)30. This technique may be useful for monitoring disease progression and treatment response in rheumatoid arthritis.

Albumins↗
PubMed1999

Prostate cancer tumor grade differentiation with dynamic contrast-enhanced MR imaging in the rat: comparison of macromolecular and small-molecular contrast media--preliminary experience.

PURPOSE: To differentiate prostate cancers of different histopathologic grades with dynamic gadolinium-enhanced magnetic resonance (MR) imaging. Results with a conventional small-molecular contrast medium (CM) were compared to those with a prototypic macromolecular CM. MATERIALS AND METHODS: High- and low-grade tumors, sublines of the Dunning R3327 rat prostate cancer line, were subcutaneously implanted into the flanks of 12 male Copenhagen rats. Dynamic contrast material-enhanced MR imaging was performed with small-molecular CM and macromolecular CM at an interval of 1 day. Microvascular permeability, as estimated with the endothelial transfer coefficient, and fractional plasma volume were calculated for each tumor and each CM by means of a two-compartmental, bidirectional kinetic model. RESULTS: Mean endothelial transfer coefficient values for both macromolecular CM and small-molecular CM were significantly different between the two tumor sublines (P = .0004 and P = .01, respectively). For the high- and low-grade tumors, no overlap of values was seen with macromolecular CM, but a broad overlap was seen with small-molecular CM despite a significant difference in mean values. CONCLUSION: Dynamic contrast-enhanced MR imaging permits differentiation of histopathologic prostatic tumor types. Quantitative microvascular permeability characteristics estimated from macromolecular CM-enhanced data were significantly superior to those derived from small-molecular CM-enhanced data.

Adenocarcinoma↗
PubMed1999

Cystic fibrosis: CT assessment of lung involvement in children and adults.

PURPOSE: To compare a computed tomographic (CT)-based scoring system with nonimaging indexes of pulmonary status in patients with cystic fibrosis. MATERIALS AND METHODS: Pulmonary CT findings were assessed in 117 patients with cystic fibrosis, with cases classified according to three groups by age; 0-5 years, 6-16 years, and 17 years and older. Images were examined for specific abnormalities, and the severity and anatomic extent of each sign were used to generate a score. Scores in each category and the global score for each patient were correlated with pulmonary function test results, clinical status, serum immunoglobulin levels, and genotype, all obtained within 2 weeks of CT. RESULTS: The most frequent individual CT abnormalities were bronchiectasis in 94 (80.3%), peribronchial wall thickening in 89 (76.1%), mosaic perfusion in 71 (63.9%), and mucous plugging in 56 (51.3%) patients. The percentage of patients with specific CT findings and the overall CT scores increased significantly (P < .05) with progressively increasing age groups. All CT findings and the overall CT scores correlated significantly (P < .05) with the pulmonary function test results, serum immunoglobulin levels, and clinical scores. No relationship was observed between genotype and CT scores. CONCLUSION: Scoring of CT studies in patients with cystic fibrosis seems to offer a reliable way to monitor disease status and progression and may provide a reasonable tool to assess treatment interventions.

Adolescent↗
PubMed1998

Quantification of the extraction fraction for gadopentetate across breast cancer capillaries.

To quantify the extraction fraction, E, for gadopentetate across tumor capillaries, R3230 adenocarcinomas were implanted in the mammary fat pads of seven rats. The value of E was determined by using a two-compartment tissue model in which the endothelial transfer coefficient, K(PS) (ml x min(-1) x cc(-1) of tissue), was estimated from the model fitted to changes in R1 relaxation time (deltaR1; s(-1)) measured by dynamic three-dimensional spoiled gradient recalled magnetic resonance imaging after injection of 0.1 mmol x kg(-1) of gadopentetate dimeglumine. The plasma flow rate through the tumor capillaries, Fp, (ml x min(-1) x g(-1) of tissue), was independently measured with fluorescent microspheres. E could be calculated by the relationship, E = K(PS)/Fp. The mean E for gadopentetate in the R3230 tumor was 0.197 +/- 0.118 with a range of 0.123-0.454. The relatively small mean value of E for gadopentetate allows a fair approximation of the permeability surface area product by K(PS) in this R3230 tumor model.

Animals↗
PubMed1998

Correlation of dynamic contrast-enhanced magnetic resonance imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media.

BACKGROUND: The endothelial integrity of microvessels is disrupted in malignant tumors. Quantitative assays of tumor microvascular characteristics based on dynamic magnetic resonance imaging (MRI) were correlated with histopathologic grade in mammary soft tissue tumors. MATERIALS AND METHODS: A spectrum of tumors, benign through highly malignant, was induced in 33 female rats by administration of N -ethyl-N -nitrosourea (ENU), a potent carcinogen. Dynamic contrast-enhanced MRI was performed using a small-molecular contrast medium [gadopentetate, MW = 0.5 kDa] and a macromolecular contrast medium [albumin-(Gd-DTPA)30, MW = 92 kDa] at an interval of 1-2 days. Permeability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (KPS), and fractional plasma volume (fPV) were calculated for each tumor and each contrast agent using a two-compartment bi-directional kinetic model. MRI microvascular characteristics were correlated with histopathologic tumor grade. RESULTS: Tumor permeability to macromolecular contrast medium, characterized by KPS, showed a highly positive correlation with tumor grade (r 2 = 0.76, P < 10(-10)). KPS values were zero for all benign and some low-grade carcinomas, greater than zero in all other carcinomas, and increased in magnitude with higher tumor grade. A considerably smaller but significantly positive correlation was found between fPV and tumor grade using macromolecular contrast medium (r 2 = 0.25, P < 0.003). No correlation between KPS or fPV values and tumor grade was found using gadopentetate (r 2 = 0.01, P > 0.95 and r2 = 0.03, P > 0.15, respectively). CONCLUSION: Quantitative tumor microvascular permeability assays generated with macromolecular MRI contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate.

Albumins↗
PubMed1998

Airway obstruction in pediatric patients. From croup to BOOP.

Causes for airways obstruction in infants and children vary considerably from those encountered in adult populations. The recent dissemination of rapid CT scan (helical and electron beam) has changed the diagnostic imaging approach in children with suspected airways obstruction. Fast CT scan not only detects the location of obstruction with high sensitivity but also frequently provides clues to specific pathologic diagnoses.

Adult↗
PubMed1998

Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media.

OBJECTIVE: The endothelial integrity of microvessels is disrupted in malignant tumors. Quantitative assays of tumor microvascular characteristics based on dynamic MR imaging were correlated with histopathologic grade in mammary soft-tissue tumors. MATERIALS AND METHODS: A spectrum of tumors, benign through highly malignant, was induced in 33 female rats by administration of N-ethyl-N-nitrosourea, a potent carcinogen. Dynamic contrast-enhanced MR imaging was performed using a small-molecular contrast medium (gadopentetate, molecular weight = 0.5 kDa) and a macromolecular contrast medium (albumin-(Gd-DTPA)30, molecular weight = 92 kDa) at an interval of 1-2 days. Permeability surface area product (PS), as estimated by the corresponding endothelial transfer coefficient (K(PS)), and fractional plasma volume (fPV) were calculated for each tumor and each contrast agent using a two-compartment bidirectional kinetic model. MR imaging microvascular characteristics were correlated with histopathologic tumor grade. RESULTS: Tumor permeability to macromolecular contrast medium, characterized by K(PS), showed a highly positive correlation with tumor grade (r2 = .76, p < 10(-10)). K(PS) values were zero for all benign and some low-grade carcinomas, greater than zero in all other carcinomas, and increased in magnitude with higher tumor grade. A considerably smaller but significantly positive correlation was found between fPV and tumor grade using macromolecular contrast medium (r2 = .25, p < .003). No correlation between K(PS) or fPV values and tumor grade was found using gadopentetate (r2 = .01, p > .95 and r2 = .03, p > .15, respectively). CONCLUSION: Quantitative tumor microvascular permeability assays generated with macromolecular MR imaging contrast medium correlate closely with histologic tumor grade. No significant correlation is found using small-molecular gadopentetate.

Albumins↗
PubMed1998

Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor.

Macromolecular contrast medium-enhanced magnetic resonance imaging (MRI) and tumor-volume measurements were applied to monitor the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody on microvascular characteristics and tumor growth of MDA-MB-435 human breast cancer cells implanted in nude rats. Administration of anti-VEGF antibody (three 1 mg doses at 3-day intervals) induced significant reductions in tumor growth rates (p < 0.05) and in MRI-assayed microvascular permeabilities (p < 0.05). Results of the study were consistent with previous observations that new microvessels formed in response to angiogenesis are hyperpermeable, and with the hypothesis that hyperpermeability is a mechanistic element in angiogenesis. Variations in tumor-vessel hyperpermeability can be measured by contrast-enhanced MRI, which may prove useful for assessing antiangiogenesis therapy.

Adenocarcinoma↗
PubMed1997

A MRI spatial mapping technique for microvascular permeability and tissue blood volume based on macromolecular contrast agent distribution.

A rapid and automated method for two-dimensional spatial depiction (mapping) of quantitative physiological tissue characteristics derived from contrast enhanced MR imaging was developed and tested in disease models of cancer, inflammation, and myocardial reperfusion injury. Specifically, an established two-compartment kinetic model of unidirectional mass transport was implemented on a pixel-by-pixel basis to generate maps of tissue permeability surface area product (PS) and fractional blood volume (BV) based on dynamic MRI intensity data after administration of albumin-(Gd-DTPA)30, a prototype macromolecular contrast medium (MMCM) designed for blood pool enhancement. Maps of PS and BV in disease models of adenocarcinoma, intramuscular abscess inflammation, and myocardial reperfusion injury clearly depicted zones of increased permeability (up to approximately 500 microl/cc/h--compared to <25 microl/cc/h in normal tissues). As revealed on PS maps, the rank ordering of studied permeability abnormalities was reperfusion injury > inflammation > tumors. A rapid, automated mapping technique derived from dynamic contrast-enhanced MRI data can be used to facilitate the identification and characterization of pathophysiologic abnormalities, specifically relative increases in blood volume and/or microvascular permeability.

Abscess↗
PubMed1997

[Macromolecular contrast media for MR mammography. A new approach to characterizing breast tumors].

The value of macromolecular contrast agents (MMCM) for the characterization of benign and malignant breast tumors will be demonstrated in this review. Animal studies suggest a high potential of MMCM to increase the specificity of MR-mammography. The concept of tumor differentiation is based on the pathological hyperpermeability of microvessels in malignant tumors. MMCM show a leak into the interstitium of carcinomas, whereas they are confined to the intravascular space in benign tumors. Capabilities and limitations of the MMCM-prototype. Albumin-Gd-DTPA, for breast tumor characterization will be summarized and compared to the standard low molecular weight contrast agent Gd-DTPA. Initial experience with new MMCM, such as Dendrimers, Gd-DTPA-Polylysine and MS-325 will be outlined. The potential of "blood-pool"-iron oxides, such as AMI-227 for the evaluation of tumor microvascular permeabilities will be discussed.

Breast↗
PubMed1997

Influence of severity of myocardial injury on distribution of macromolecules: extravascular versus intravascular gadolinium-based magnetic resonance contrast agents.

OBJECTIVES: This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns. BACKGROUND: Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity). METHODS: To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesla system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing. RESULTS: Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA-enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/ normal myocardium increased with increasing duration of ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin-enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (overall p value < 0.0001, ANOVA). CONCLUSIONS: At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.

Albumins↗
PubMed1997

Definition of liver tumors in the presence of diffuse liver disease: comparison of findings at MR imaging with positive and negative contrast agents.

PURPOSE: The potential to define liver tumors at magnetic resonance (MR) imaging was compared with a positive and a negative contrast agent (gadoxetic acid disodium, or gadolinium EOB-DTPA [a hepatocyte-directed agent], and ferumoxides, or superpara-magnetic iron oxide particles [a Kupffer cell-directed agent], respectively) in normal rats and in rats with induced acute hepatitis, fatty liver, or cirrhosis. MATERIALS AND METHODS: Rats with implanted liver adenocarcinomas were divided into four groups: no diffuse liver disease ("normal" [n = 6]) and diffuse liver diseases (induced acute hepatitis [n = 6], fatty liver [n = 6], or cirrhosis [n = 6]). Rats first received gadoxetic acid disodium (50 mumol/kg) and then, 45 minutes later, ferumoxides (10 mumol/kg). Liver signal intensity enhancement and tumor-to-liver contrast-to-noise ratio (C/N) were measured in each group. RESULTS: Mean liver signal intensity enhancement values with gadoxetic acid disodium and ferumoxides were excellent in the normal liver model (176% and -62%, respectively; P < .01) but were significantly reduced in the acute hepatitis model (82% and -36%, respectively). In the fatty livers compared with the normal livers, enhancement with gadoxetic acid disodium was reduced (57%) but with ferumoxides was excellent (-55%). In the cirrhotic livers compared with the normal livers, enhancement with gadoxetic acid disodium (174%) was virtually the same but was impaired with ferumoxides (-43%). CONCLUSION: Hepatic enhancement and tumor-to-liver C/N with either positive or negative liver-enhancing agents can be impaired by the presence of underlying liver disease. Prior knowledge of the type of diffuse liver disease may influence the choice of contrast agent for tumor detection.

Acute Disease↗
PubMed1997

Arthritic temporomandibular joint: correlation of macromolecular contrast-enhanced MR imaging parameters and histopathologic findings.

PURPOSE: To assess the utility of macromolecular contrast material-enhanced magnetic resonance (MR) imaging parameters for determining the histopathologic severity of temporomandibular joint (TMJ) arthritis. MATERIALS AND METHODS: Ovalbumin was used to induce arthritis in the TMJs of 10 previously sensitized adult white rabbits. Five rabbits composed the sham-treated control group. Dynamic spin-echo imaging was performed immediately before and for 30 minutes after injection of macromolecular contrast medium. Histologic specimens of TMJ were assessed quantitatively for arthritis. Changes in MR signal intensity were derived from the synovial and subsynovial tissues of the TMJ, and plasma volume (PV) and permeability surface area product (PS) were calculated. These MR parameters and the arthritic scores were compared between sham-treated and antigen-challenged TMJs. The relationships between MR parameters and histopathologic indexes were also determined. RESULTS: Arthritic TMJs showed marked enhancement of the synovial and subsynovial tissues over the imaging period. PS and all histopathologic indexes of arthritis were significantly greater (P < .005) in antigen-challenged than in sham-treated TMJs. PS demonstrated strong positive relationships with all histologic parameters of arthritis, indicating its utility for assessing the severity of joint inflammation. CONCLUSION: Macromolecular contrast-enhanced MR imaging enables quantification of PS and PV in inflamed joints. This technique may provide insights into the pathogenesis of joint inflammation and noninvasive monitoring of disease severity and treatment response in arthritis.

Albumins↗