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M F Wendland

Publications and source records attributed to M F Wendland.

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

Tumor blood volume assays using contrast-enhanced magnetic resonance imaging: regional heterogeneity and postmortem artifacts.

Tumor blood volume (BV), subject to both morphologic and physiologic influences, can be measured using contrast-enhanced magnetic resonance imaging (MRI). The aims of this study were to determine whether MRI enhanced with a macromolecular contrast medium (MMCM) could resolve differences in BV between different tumor types, between different regions within tumors, and within the same tumor in life and after death. Tumor BV estimates were based on the MRI signal intensity responses in the tumors and in reference venous blood following enhancement with a blood pool MMCM using two mammary adenocarcinoma models. Estimates of BV were made before and immediately following death. An in vitro measurement of tumor gadolinium concentration following death was correlated with MRI enhancement. Statistically significant differences (P < 0.05) were observed in MRI-estimated tumor BV between tumor subtypes, between in vivo and postmortem measurements, and between the tumor periphery and tumor centers. MRI assays enhanced with a macromolecular contrast agent can resolve blood volume differences between tumor types, between regions within the same tumor, and between vital and postmortem states.

Albumins↗
PubMed1999

Contrast-enhanced MRI for quantification of myocardial viability.

During the past 10 years substantial advances have taken place in magnetic resonance imaging (MRI) capabilities and in contrast media development. Furthermore, knowledge of in vivo contrast media interactions with surrounding water and distribution into tissue has increased, permitting regional quantification of concentration-time profiles in the myocardium. The combination of these advances has substantially improved the capability of contrast-enhanced MRI characterization of myocardial ischemic injury, including its ability to discriminate viable from nonviable zones. Discrimination of viable from nonviable myocardial subregions is important for patient management and for research applications. This review addresses recent progress toward the goal of defining viable and nonviable myocardium based on MRI detection of contrast media effects. J. Magn. Reson. Imaging 1999;10:694-702.

Animals↗
PubMed1999

Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats.

PURPOSE: To measure the fractional distribution volume of gadopentetate dimeglumine in normal and reperfused infarcted myocardium at magnetic resonance (MR) imaging by using the fractional distribution volume of technetium 99m-diethylenetriaminepentaacetic acid (DTPA) as an independent reference. MATERIALS AND METHODS: Rats were subjected to 1 hour of coronary artery occlusion and 1 hour of reperfusion before inversion-recovery echo-planar imaging or autoradiography. Regional change in relaxation rate (delta R1) ratios for myocardium over blood were compared with radioactivity ratios for myocardium over blood after the injection of 99mTc-DTPA. RESULTS: Both delta R1 and radioactivity ratios demonstrated equilibrium distribution and hence represent partition coefficients (lambda). The fractional distribution volumes were greater in infarcted myocardium (0.90 +/- 0.05 for gadopentetate dimeglumine and 0.89 +/- 0.04 for 99mTc-DTPA) than in normal myocardium (0.23 +/- 0.02 for gadopentetate dimeglumine and 0.16 +/- 0.01 for 99mTc-DTPA). Area at risk at autoradiography was not significantly different from that at histomorphometry. The infarction size defined by using triphenyltetrazolium chloride was 13% +/- 4 smaller than that defined by using autoradiography. CONCLUSION: The fractional distribution volumes of gadopentetate dimeglumine and 99mTc-DTPA are similar and indicate extracellular distribution in normal myocardium and intracellular as well as extracellular distribution in reperfused infarction. Because the failure of cells to exclude these agents is indicative of necrosis, contrast medium-enhanced MR imaging may be useful to quantify myocardial infarction.

Animals↗
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

Reperfused myocardial infarction as seen with use of necrosis-specific versus standard extracellular MR contrast media in rats.

PURPOSE: To measure the difference in size of reperfused myocardial infarction with necrosis-specific (bis-gadolinium-mesoporphyrin [hereafter, mesoporphyrin]) and standard extracellular (gadopentetate dimeglumine) magnetic resonance (MR) contrast media. MATERIALS AND METHODS: Echo-planar (for T1 measurement) and spin-echo (for infarction size) MR imaging were conducted in 32 rats subjected to reperfused reversible (n = 16) and irreversible (n = 16) myocardial injuries. All animals received gadopentetate dimeglumine 1 hour after reperfusion and underwent imaging. Sixteen rats received mesoporphyrin at 2 hours, the other 16 rats received gadopentetate dimeglumine at 24 hours, and all animals underwent imaging at 24 hours. RESULTS: Mesoporphyrin produced prolonged (22 hours) reduction in T1 in irreversibly, but not in reversibly, injured myocardium. The size of the mesoporphyrin-enhanced region (37% +/- 4 [SEM] of left ventricular surface area) closely correlated with the true infarction size as measured by means of histomorphometry (36% +/- 3, r = 0.90). The size of the gadolinium-enhanced region overestimated (48% +/- 2 and 43% +/- 1 at 1 and 24 hours of reperfusion, respectively) the size of true infarction (36% +/- 3, P < .05, r = 0.02), but it was close to the size of the area at risk (r = 0.93). CONCLUSION: The sizes of hyperenhanced regions displayed by using mesoporphyrin and gadopentetate dimeglumine differed from each other. The difference in size of the hyperenhanced region demarcated by mesoporphyrin and gadopentetate dimeglumine may provide an estimation of potentially salvageable myocardium.

Animals↗
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

Value of blood pool contrast agents in magnetic resonance angiography of the pelvis and lower extremities.

Our objective was: (1) to determine the appropriate dose of new ultrasmall superparamagnetic iron oxide particles for magnetic resonance angiography (MRA). This agent comprised of a single iron oxide crystal stabilized with a carbohydrate-polyethylene glycol coat (PEG-Ferron/NC 100150 injection); (2) to determine the proper flip angle for PEG-Ferron-enhanced 3 D time-of-flight (TOF) MRA sequence; and (3) to compare the enhancement of peripheral vessels following PEG-Ferron and GdDTPA-BMA. MRA parameters were: TR/TE = 50/2.1 ms, NEX = 1, FOV = 30 x 30 x 1.8 cm, and matrix = 256 x 128 x 64. In anesthetized beagle dogs (n = 10), the effects of PEG-Ferron and GdDTPA-BMA on regional signal were monitored for 45 min and compared. The lowest dose of PEG-Ferron (0.05 mmol/kg) produced the best enhancement of primary, secondary and tertiary vessels. The flip angle 60 degrees provided better enhancement than 20 degrees on contrast enhanced images. Unlike GdDTPA-BMA, PEG-Ferron allowed prolonged delineation (> 45 min) of the pelvis and lower extremities circulation. PEG-Ferron provided greater Contrast-to-noise ratio CNR (80.2 +/- 6.2, P < 0.05) than GdDTPA-BMA (63.5 +/- 2.5). It may be possible for blood pool contrast-enhanced 3 D TOF MRA to provide valuable information for visualization of vascular tree including guiding interventions.

Animals↗
PubMed1998

Microvascular injury in reperfused infarcted myocardium: noninvasive assessment with contrast-enhanced echoplanar magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to measure the accumulation of labeled albumin and to visualize its distribution pattern in reperfused infarcted myocardium as a function of time between onset of reperfusion and administration of the tracer. BACKGROUND: Myocardial microvascular injury leads to leakage of albumin from the intravascular space. Quantitative measurements of GdDTPA-albumin with inversion recovery echoplanar imaging (IR-EPI) may allow noninvasive monitoring of microvascular injury. METHODS: After 1 h of coronary artery occlusion, 56 rats were injected with GdDTPA-albumin or 123I-GdDTPA-albumin either immediately before reperfusion or 1/2, 1 or 24 h after reperfusion. GdDTPA-albumin in blood, normal myocardium and reperfused infarction was dynamically measured with IR-EPI during 1 h postinjection (PI). Autoradiograms were obtained at 15 min PI. Accumulation of labeled albumin in myocardium was expressed as the ratio of myocardial to blood content. RESULTS: In normal myocardium, the ratio of changes of relaxation rate-ratio (deltaR1-ratio) was 0.12+/-0.01 and did not change over 1 h. In reperfused infarction, however, the deltaR1-ratio increased after administration. Animals given GdDTPA-albumin before reperfusion exhibited fastest accumulation (deltaR1-ratio 15 min PI: 0.56+/-0.03) and essentially homogeneous distribution. The accumulation was slower when administered at 1/2, 1 and 24 h after reperfusion (deltaR1-ratios 15 min PI: 0.39+/-0.03; 0.31+/-0.04; 0.16+/-0.01; p < 0.001 compared to administration before reperfusion). Moreover, the tracer accumulated predominantly in the periphery of the injury zone. CONCLUSIONS: Amount and distribution pattern of labeled albumin in reperfused infarction are modulated by duration of reperfusion. The accumulation of GdDTPA-albumin can be quantified by IR-EPI. Thus, IR-EPI may be useful to noninvasively monitor myocardial microvascular injury in reperfused infarction.

Albumins↗
PubMed1998

Depiction of reperfused myocardial infarction using contrast-enhanced spin echo and gradient echo magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors used gadolinium (Gd) chelate as a T1, T2, and T2* enhancing agent in reperfused myocardial infarction to compare the appearance of reperfused myocardial infarction on spin echo and gradient echo magnetic resonance (MR) sequences. METHODS: Rats (n = 28) were subjected to reperfused myocardial infarction and received no contrast medium, 0.2, 0.5, or 1.0 mmol/kg Gd DTPA-BMA. Spin echo and gradient echo MR images of the excised hearts (n = 7 rats per group) were acquired using 2.0 T system: repetition time (TR)/echo time (TE) = 300/20 ms for T1-weighted spin echo, TR/TE = 4000/80 ms for T2-weighted spin echo, and TR/TE = 600/10, 15, 20, and 30 ms for gradient echo imaging. Regional T2 and T2* relaxation times were measured. Triphenyl tetrazolium chloride was used to verify regional infarction. RESULTS: Unenhanced spin echo images failed to distinguish infarcted from normal myocardium. On Gd DTPA-BMA enhanced T1-weighted spin echo images, infarction was depicted as a high-intensity region "hot spot." On the other hand, the infarcted region was visualized as a low-signal region "cold spot" on Gd DTPA-BMA enhanced T2-weighted images. Changes in signal intensity and T2 relaxation time on T2 weighted images were dose dependent. On gradient recalled echo images, the infarcted region was discriminated from normal myocardium by a dark boundary zone, which was visible only at 1.0 mmol/kg. The presence of infarction was documented in every heart. CONCLUSIONS: The contrast between normal and infarcted myocardium was affected greatly by the dose and imaging parameters. The results indicate that spin echo and gradient echo images have greatly differing sensitivities to extracellular gadolinium chelates. Changes in myocardial T2 relaxation time, but not T2*, correlated well with the dose.

Animals↗
PubMed1998

Osteogenic sarcoma: noninvasive in vivo assessment of tumor necrosis with diffusion-weighted MR imaging.

PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for detecting tumor necrosis in an animal model of osteogenic sarcoma. MATERIALS AND METHODS: Twelve rats with osteogenic sarcoma underwent T1-weighted unenhanced and gadolinium-enhanced spin-echo and diffusion-weighted spin-echo MR imaging. Histologic correlation was performed. Signal intensities, T2 relaxation times, normalized apparent diffusion coefficients, and relative signal intensity increases were calculated. RESULTS: On diffusion-weighted images, necrotic tumor showed low signal intensity (mean normalized apparent diffusion coefficient, 0.46 +/- 0.20 [1 standard deviation]), indicating rapid diffusion of water molecules as a result of loss of membrane integrity, while viable tumor showed high signal intensity (mean normalized apparent diffusion coefficient, 0.16 +/- 0.05; P < .0001). Differences in the T2 relaxation times and relative signal intensity increases between viable and necrotic tumor were not statistically significant. CONCLUSION: Normalized apparent diffusion coefficients are more accurate in differentiating between viable and necrotic tumor than are T2 relaxation times or relative signal intensity increases on contrast-enhanced images. Signal intensity overlap between viable and necrotic tumor on gadolinium-enhanced images may be caused by the small molecular size of the agent, which permeates the interstitial space freely, thereby also enhancing necrosis. Diffusion-weighted MR imaging depicts differences in diffusion and, ultimately, in membrane integrity between viable and necrotic tumor and may be used to monitor tumor viability during treatment.

Animals↗
PubMed1997

Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI.

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). delta R1 was repeatedly measured over 30 min. Gd-BOPTA caused greater delta R1 for blood and myocardium than did Gd-DTPA; clearance of both agents from normal- and infarcted myocardium was similar to blood clearance; plots of delta R1 myocardium/delta R1 blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTPA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater delta R1 than Gd-DTPA in regions which contain serum albumin.

Animals↗
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

Quantification of coronary artery volume flow rate using fast velocity-encoded cine MR imaging.

OBJECTIVE: Breath-hold velocity-encoded cine (VENC) MR imaging has been proposed as a method for measuring coronary blood flow. However, most studies have measured velocity rather than volume flow rate in the coronary arteries. The purpose of this study was to measure volume flow rate in the coronary artery of dogs using high-speed gradients and to compare MR flow measurements with those obtained with a sonographic flowmeter. MATERIALS AND METHODS: Fast VENC MR images were obtained with a high-speed-gradient 1.5-T MR system in seven anesthetized dogs before and after administration of dipyridamole. Images were acquired on double oblique planes perpendicular to the left anterior descending arteries with a slice thickness of 5 mm, a field of view of 20 x 10 cm, a velocity window of +/- 1 m/sec, an average imaging time of 21 sec, a TR/TE of 11/5, and a temporal resolution of 44 msec. RESULTS: Coronary flow measured with VENC MR imaging correlated well with flow measured by the flowmeter (r = .95, slope = 0.97, n = 88). Interobserver variability in measuring coronary flow volume was 8%. CONCLUSION: Fast VENC MR imaging with high-speed gradients can provide accurate quantification of volume flow rate in coronary arteries.

Animals↗
PubMed1996

Quantification of the extent of area at risk with fast contrast-enhanced magnetic resonance imaging in experimental coronary artery stenosis.

Fast magnetic resonance (MR) imaging techniques have the capability of demonstrating regions of ischemia caused by stenosis. The size of the potentially ischemic area determines the importance of the stenosis. The purpose of this study was to determine the relative values of relaxivity-enhancing and magnetic-susceptibility MR contrast media in detecting and sizing the area at risk in dogs. Eight dogs were subjected to critical left circumflex coronary artery (LCX) stenosis. Sixty sequential inversion-recovery- and driven-equilibrium-prepared fast gradient recalled echo images were acquired during bolus administration of 0.03 mmol/kg gadodiamide or 0.4 mmol/kg sprodiamide in basal and vasodilated (dipyridamole-stress) states. The size of the area at risk was measured and compared with that measured post mortem. In the basal state, gadodiamide and sprodiamide equivalently altered the signal intensities of nonischemic myocardium and the territory of stenosed coronary artery. Dipyridamole produced a significant increase in left anterior descending coronary artery flow with a decrease in LCX flow. The hypoperfused region was observed as a low-and high-signal intensity region after administration of gadodiamide and sprodiamide, respectively. The size of the hypoperfused region was slightly smaller with gadodiamide (37.4% +/- 2.8%) and sprodiamide (34.0% +/- 2.2%) than the true area at risk measured post mortem (41.8% +/- 2.2%; p < 0.05). Dipyridamole perfusion MR imaging with relaxivity or susceptibility contrast media is a noninvasive method to identify and quantify the area at risk in the territory of a stenotic coronary artery. Changes in myocardial signal intensity on fast gradient recalled echo images reflect the augmentation of flow and volume induced with dipyridamole and are consistent with the "steal phenomenon."

Animals↗
PubMed1996

Verapamil reduces the size of reperfused ischemically injured myocardium in hypertrophied rat hearts as assessed by magnetic resonance imaging.

Contrast-enhanced magnetic resonance (MR) imaging was used to detect and quantify the extent of myocardial injury after a brief coronary occlusion and reperfusion in response to verapamil treatment in a rat model of left ventricular hypertrophy (LVH). Two groups of rats were prepared by banding the abdominal aorta for 7 to 8 weeks to produce LVH. Group 1 (n = 13) received oral verapamil for 3 days, whereas group 2 (n = 13) received no therapy. Before MR examination was performed, each rat was subjected to 25 min of coronary artery occlusion followed by 1 hour of reperfusion. T1-weighted spin echo images were acquired before and after 0.3 mmol/kg gadoteridol was injected. Three images were acquired at contiguous levels of the LV and used to estimate the size of the myocardial injury. The size of the infarcted region was demarcated at postmortem examination by using triphenyltetrazolium chloride dye (TTC). Before contrast medium was administered, no significant difference in signal intensity was seen between nonischemic and reperfused ischemically injured myocardium. After gadoteridol was injected, a hyperintense zone indicative of myocardial injury was observed in 8 of 13 rats treated with verapamil and in all untreated animals. The size of the injury was significantly larger in untreated hearts than in hearts treated with verapamil as defined on MR images (25% +/- 5% vs 18% +/- 5%, p < 0.05) and TTC staining (12% +/- 4% and 4% +/- 1%, p < 0.05). Good correlation (r = 0.91) was found between the two measurements. No significant difference in the size of jeopardy area was seen between the two groups as (defined by blue dye infusion). In conclusion, contrast-enhanced MR imaging is a suitable technique to evaluate the effects of therapies applied to reduce myocardial injury. Verapamil can cause reduction in the extent of ischemic injury after reperfusion of hypertrophied myocardium.

Animals↗