Relationship between the Number of SPIO-labeled Macrophage and MR Signal Intensity

PURPOSE: For the in vivo imaging of macrophages using MRI, the feasibility of labeling macrophages with iron oxide and the number of SPIO-labeled macrophage detected in 1.5 T MR, were assessed. MATERIALS AND METHODS: The MR signal intensity was measured with variable concentrations of iron oxide, ranging from 112 to 2.384x10-7 μgFe/mL. The macrophages were incubated in SPIO solution (112 μgFe/mL) for 24 hours. The MR signal intensity was measured in variable numbers of SPIO-labeled macrophages. RESULTS: The MR image signal intensity gradually increased with decreasing SPIO concentration, and reached a plateau at a concentration of 0.219 μgFe/mL. After incubation with iron oxide, the compact uptake of SPIO was detected in the cytoplasm of the macrophages using Prussian blue staining. No susceptibility effect was detected in the tubes of more than 122 macrophages. CONCLUSION: The MR signal intensity was dependent on the number of macrophages. No susceptibility effect due to a cluster of SPIO-labeled macrophages was detected in more than 488 cells.

The Effect of Micro-Particles of Linoleic Acid Emulsion on the Blood-Brain Barrier in Cats

PURPOSE: The purpose of this study was to investigate the permeability change of the blood-brain barrier and the reversibility of the embolized lesions induced with a fat-emulsion technique by using magnetic resonance imaging (MRI), and we also wished to evaluate the resultant histologic findings in cat brains. MATERIALS AND METHODS: MR imaging was scheduled serially at 1 hour, day 1, day 4 and day 7 after infusion of linoleic acid-emulsion (0.05 ml linoleic acid+20 ml saline) to the internal carotid artery in 12 cats. Abnormal signal intensity or contrast enhancement was evaluated on diffusion-weighted images (DWIs), the apparent diffusion coefficient (ADC) maps, and gadolinium-enhanced T1-weighted images (Gd-T1WIs) at the stated times. MR imaging was stopped if the lesion shows isointensity and no contrast enhancement was observed at the acquisition time, and then brain tissue was harvested and examined. Light microscopic (LM) and electron microscopic (EM) examinations were performed. RESULTS:The embolized lesions appeared as isointensities (n=7) or mild hyperintensities (n=5) on DWIs, as isointensities (n=12) on the ADC maps, and as contrast enhancements (n=12) on Gd-T1WIs at 1 hour. The lesions showed isointensity on DWIs and the ADC maps, and as no contrast enhancement for all cats at day 1. The LM findings revealed small (< 1 cm) focal necrosis and demyelination in three cats. EM examinations showed minimal findings of small (< 3 micrometer) fat globules within the endothelial wall (n=10) and mild swelling of the neuropils (< 5 micrometer). Widening of the interstitium or morphologic disruption of the endothelial wall was not seen. CONCLUSION: Cerebral fat embolism induced by linoleic acid emulsion revealed vasogenic edema and reversible changes as depicted on the MR images. These results might help us to understand the mechanisms of fat on the blood-brain barrier, and this technique could be used as a basic model for research of the effects of drugs on the disrupted blood-brain barrier, and also as a research model for the chemotherapeutic effects of drugs of the brain tumors.

Turnover in Intracranial Aneurysm Phantoms: Its Relation to Neck Size

PURPOSE: To evaluate the physiologic background of aneurysms poorly visualized during 3D-TOF MRA, contrast-enhanced MRA (CEMRA) and DSA due to hemodynamic isolation. MATERIALS AND METHODS: Using handmade elastic silicon phantoms to represent terminal basilar tip aneurysms, 3D-TOF MRA, CEMRA and DSA were used to determine blood turnover. Aneurysmal neck size was 2 mm and 10 mm, and the use of a pulsatile pump also helped recreate human physiologic parameters. We compared the results with those of computational fluid dynamics. RESULTS: DSA images of the narrow-necked aneurysm showed that a small volume of contrast medium washed into it during the systolic phase. As the width of its neck increased, the turnover volume of fragments of contrast bolus also increased. At CEMRA, the broad-necked aneurysm was visualized as the main bolus of Gd-DT PA passed through it, and at delayed CEMRA, the narrow-necked aneurysm was visualized faintly after the passage of bolus Gd-DT PA. The results correlated closely with those of 3DTOF MRA and computational fluid dynamics. CONCLUSION: The visualization of intracranial aneurysms at 3D-TOF MRA, CEMRA and DSA was greatly dependent upon blood turnover, which varied according to aneurismal neck size. A narrow-necked aneurysm might be missed at 3D-TOF MRA, CEMRA and DSA due to hemodynamic isolation.

Gadobenate Dimeglumine-enhanced MR of VX2 Carcinoma in Rabbit Liver: Usefulness of the Delayed Phase Imaging and Optimal Pulse Sequence

PURPOSE: To assess the diagnostic value of delayed imaging using gadobenate dimeglumine(MultiHance) and to determine the optimal pulse sequence for the detection of VX2 carcinoma lesions in the rabbit. MATERIALS AND METHODS: Twelve VX2 carcinomas implanted in the livers of eleven New Zealand rabbits were studied. All patients underwent an MR protocol consisting of precontrast T2-and T1-weighted sequences, followed by repetition of the T1-weighted sequence at 0 to 30 (arterial phase), 31-60 (portal phase), and 40 minutes (delayed phase) after the intravenous administration of 0.1 mmol/kg of gadobenate dimeglumine. The signal-to-noise ratio (SNR) of the liver and VX2 tumor, and the lesion-to-liver contrast-to-noise ratio (CNR) of precontrast and postcontrast MR images were quantitativlely analyzed, and two experienced radiologists evaluated image quality in terms of lesion conspicuity, artifact, mass delineation, and vascular anatomy. RESULTS: Liver SNR was significantly higher at delayed imaging than at precontrast, arterial, and portal imaging (p<0.05), while lesion SNR was significantly higher at delayed imaging than at precontrast imaging (p<0.05). Lesion CNR was higher at delayed imaging than at precontrast and portal phase imaging (p<0.05), but there was no difference between arterial and delayed imaging. The latter provided better mass delineation than precontrast, arterial and portal phase imaging (p<0.05). While in terms of lesion conspicuity and vascular anatomy, the delayed phase was better than the arterial phase (p<0.05) but similar to the precontrast and portal phase. During the delayed phase, the gradient-echo sequence showed better results than the spin-echo in terms of liver SNR, and lesion SNR and CNR (p<0.05). CONCLUSION: Because it provides better lesion conspicuity and mass delineation by improving liver SNR and lesion-to-liver CNR, the addition of the delayed phase to a dynamic MRI sequence after gadobenate dimeglumine administration facilitates lesion detection. For delayed-phase imaging, the gradient-echo sequence is superior to the spin-echo sequence.

Quantification of Dextrose in Model Solution by H MR Spectroscopy at 1.5T

PURPOSE: To evaluate the feasibility of proton magnetic resonance spectroscopy (1H-MRS) using a 1.5T magnetic resonance (MR) imager for quantification of the contents of model solutions. MATERIALS AND METHODS: We prepared model solutions of dextrose+water and dextrose+water+ethanol at dextrose concentrations of 0.01% to 50% and 0.01% to 20%, respectively. Using these solutions and a 1.5T MR imager together with a high-resolution nuclear magnetic resonance (NMR) spectroscope, we calculated the ratios of dextrose to water peak, (dextrose+ethanol) to water peak, and (dextrose+ethanol) to ethanol peak, as seen on MR and NMR spectra, analysing the relationships between dextrose concentration and the ratios of peaks, and between the ratios of the peaks seen on MR spectra and those seen on NMR spectra. RESULTS: Changes in the ratios between dextrose concentration and dextrose to water peak, (dextrose+ethanol) to water peak and (dextrose+ethanol) to ethanol peak, as seen on MR spectra, were statistically significant, and there was good linear regression. There was also close correlation between the ratios of the observed on MR and NMR spectra. The results depict the quantification of dextrose concentration according to the ratios of spectral peaks obtained by proton MRS at 1.5T. CONCLUSION: Using proton MRS at 1.5T, and on the basis of the ratios of spectcal peaks, it was possible to quantify the concentration of dextrose in model solutions of dextrose+water and dextrose+water+ethanol. The results of this study suggest that for quantifying the contents of biofluids, the use of low-tesla 1H-MRS is feasible.

Reversal of Apparent Diffusion Coefficient (ADC) Following Transient Focal Cerebral Ischemia in Cats

PURPOSE: To determine the minimal threshold ADC ratio suggesting reversible ischemia in a temporary model of MCAO. MATERIALS AND METHODS: Seven Korean cats weighing 3-3.5 kg were used as a temporary model of MCAO. The MCA was occluded for 1 hour, and diffusion-weighted images (DWI), and ADC and regional cerebral blood volume (rCBV) maps, were obtained at 1, 3, 6 and 24 hours after reperfusion using a 1.5T MR unit. The Cats were sacrificed 24 hours after imaging. Triphenyl tetrazolium chloride (TTC) staining of brain slices was performed, and DWI images and TTC-stained brain slices were compared with the naked eye. Reversible ischemia was defined as the area of high signal intensity at 1-hour DWI that normalized at follow-up DWI and in which TTC staining was normal. Using the ADC image obtained at 1 hour after reperfusion, 60 ADC ratios were obtained in the periphery of the infarct and reversible ischemia. Tissue survival showing normal TTC staining was used for final determination. The sensitivity and specificity of each ADC ratio was obtained and an ROC curve was plotted. RESULTS: Five of seven cats showed the reversible ischemia. An area of high signal intensity was seen on DWI images obtained 1 hour after reperfusion, and this improved at follow-up imaging. The distribution of the ADC ratio in the periphery of the infarct core was 0.71-0.81, and in the periphery of reversible ischemia it was 0.79-0.93. The ADC ratio of 0.80 obtained 1 hr after reperfusion predicted the survival of the ischemic tissue with 93% sensitivity and 90% specificity. The ADC ratio of the reversible ischemia was 0.82+/-0.03 at 1 hour after reperfusion, and this was higher than that of the infarct, which was 0.74+/-0.03. CONCLUSION: The minimal threshold ADC ratio suggesting reversible ischemia in this temporary model of MCAO was 0.80.

Magnetic Resonance Imaging and Histologic Findings of Acute and Subacute Stage of Experimental Cerebral Fat Embolism in Cats

PURPOSE: To determine the magnetic resonance imaging (MRI) findings and natural history of cerebral fat embolism in a cat model, and to correlate the MRI and histologic findings. MATERIALS AND METHODS: Using the femoral arterial approach, the internel carotid artery of 11 cats was injected with 0.1 ml of triolein. T2-weighted (T2WI), T1-weighted (T1WI) and Gd-enhanced T1-weighted (Gd-T1WI) images were obtained serially at 2 hours, 1 and 4 days and 1, 2 and 3 weeks after embolization. Any abnormal signal intensity (SI) was evaluated. After MR imaging at 3 weeks, brain tissue was obtained for light microscopic (LM) examination using hematoxylin-eosin and Luxol fast blue staining, and for electron microscopic (EM) examination. The histologic and MRI findings were correlated. RESULTS: At 2 hours, lesions showed high SI at T2WI, iso- or low SI at T1WI, and strong enhancement at Gd-T1WI. The high SI seen at T2WI decreased thereafter, and most lesions became iso-intense. At week 3, however, small focal areas of high SI were seen in the grey matter of eight cats and in the white matter of three. The low SI noted at acute-stage T1W1 subsequcntly became normal, though in the areas in which T2W1 had depicted high SI, focal areas of low SI remained. Lesion enhancement demonstrated by Gd-T1WI decreased continuously from day 1, and at week 3, weak enhancement was seen at the margin of the remained hypointense lesions in the gray matter in five cats. At LM examination with hematoxylin-eosin staining revealed normal histologic findings in the greater park of an embolized lesion. Cystic change was observed in the gray matter of eight cats, and in the gray and white matter of three of the eight. At LM examination, Luxol fast blue, staining demonstrated demyelination around the cystic change occurring in the white matter, and EM examination of the embolized cortex revealed sporadic intracapillary fat vacuoles (n=11) and disruption of the blood-brain barrier (n=4). Most lesions were normal, however, and perivascular interstitial edema and cellular swelling were mild compared with the control side. CONCLUSION: Experimental cerebral fat embolism was clearly demonstrated by T2WI and Gd-T1WI images obtained at all time points. The greater part of an embolized lesion showed reversible findings at MR and histologic examination; irreversible focal necrosis was, however, observed in gray and white matter at week 3.

Influence of Mn-DPDP on MRI and Proton MR Spectroscopy of the Liver

PURPOSE: To determine the influence of manganese dipyridoxyl diphosphate (Mn-DPDP) on MRI and proton MRS. MATERIALS AND METHODS: In an in-vitro study designed to determine changes in the lipid peak at 1.3 ppm, 4.7T MR equipment was used to obtain proton MR spectrographic images of a lipid solution of varying concentration, with and without Mn-DPDP. Before; at 10, 20, and 30 minutes; and at 1, 2, 4, and 24 hours after the IV injection of Mn-DPDP (10umol, 1ml/kg), the concentration of Mn in liver tissue was measured by atomic absorption spectrometry. At the same intervals, T1-weighted MR images were obtained, the signal intensity ofthe liver was thus determined, and the relative enhancement ratio was calculated. MRS of rabbit liver was performed serially at the same intervals, and the peak areas of metabolites, as well as their peak areas relative to lipids, were calculated. The findings were correlated with tissue Mn concentration. RESULTS: At 1.3 ppm with Mn-DPDP, MRS showed that the peak area of the lipid had decreased. Tissue Mn concentration increased just after Mn-DPDP injection and peaked after 20 minutes, decreasing to a level within the normal range after 24 hours. Serial changes in the signal intensity of the liver, as seen at MRI, showed a similar pattern to that of Mn concentration. There was reverse correlation between serial change in the peak area of lipids at 1.3 ppm and Mn concentration after Mn-DPDP injection. CONCLUSION: At T1-weighted MR imaging, the injection of Mn-DPDP led to the enhancement of liver tissue, and at MRS, the lipid peak at 1.3 ppm decreased. There was close correlation between these effects and tissue Mn concentration.

Diffusion-Weighted MR Imaging in Animal Model with Acute Ischemic Brain Infarction: Evaluation of Reversible Brain Injury

PURPOSE: To determine whether the analysis of abnormally high signal intensities in ischemic tissue, as revealed by diffusion-weighted MR imaging (DWI) can be used to evaluate reversible brain lesions in a cat model of acute ischemia. MATERIALS AND METHODS: Ten cats were divided into two groups of five (Group I and Group II), and in all animals the middle cerebral artery was temporarily occluded. Group I underwent T2-DWI 30 minutes after occlusion, and Group II 120 minutes after occlusion. In both groups, DWI was performed one hour and 24 hours after reperfusion (at one hour, non-T2-weighted; at 24 hours, T2-weighted). Both occlusion and reperfusion were monitored by 99m TC-ECD brain perfusion SPECT. All animals were sacrificed 24 hours later and their brain tissue was stained with TTC. Signal intensity ratios (SIR, signifying average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region) of the two groups, as seen on DWI were compared. The percentage of hemispheric lesions occurring in the two groups was also compared. RESULTS: SIR after occlusion of the middle cerebral artery was 1.29 in Group I and 1.59 in Group II. Twenty-four hours after reperfusion, SIR in Group I was higher than in Group II (p<0.01). After occlusion and reperfusion, the percentage of hemispheric lesions in Group I was less than in Group II. For the latter, the percentage of these lesions revealed by TTC staining and T2-weighted imaging was 48% and 59%, respectively, findings distinctly different from those for Group I. In addition, in group I, infarction was revealed by neither TTC staining nor T2-weighted imaging (p<0.01). CONCLUSION: The use of DWI to evaluate signal intensity ratios can help determine whether or not brain injury after temporary cerebral ischemia is reversible.

Proton MR Spectroscopic Features According to Change of Hepatic Parenchymal Iron Content after SPIO Injection

PURPOSE: To determine the effect of iron on proton MR spectra (1H-MRS) by evaluating changes in 1H-MRS of the liver according to changes in hepatic parenchymal iron content. MATERIALS AND METHODS: We evaluated serial changes in 1H-MRS of the liver after intravenous infusion of SPIO in 40 rabbits. These were divided into eight groups of five, and in each group, respectively, 1H-MRS and T2WI MR images were acquired prior to SPIO infusion, just after infusion, and at 15 minutes and 1, 2, 4, 24 and 96 hours after infusion. MR spectra were evaluated with particular attention to the curve pattern observed at specific times after the infusion of SPIO, and the results were correlated with the signal intensity observed on T2W1 images and the histologic giade of ilon content of samples of resected liver parenchyma. RESULTS: As observed on T2WI, the mean signal intensity of rabbit liver in its pre-SPIO infusion state, just after infusion, at 15 minutes, and at 1, 2, 4, 24 and 96 hours after SPIO infusion was 121.3 +/-15.5, 41.5 +/-12.7, 30.3 +/-7.9, 31.3 +/-3.5, 33.6 +/-9.4, 45.5 +/-10.9, 80.3 +/-15.7 and 110.4 +/-22.9, respectively(p<0.05). Mean standard deviation of the ratio of the area of the peak (3.9-4.1 ppm) / lipid peak (1.3 ppm) peak at each of the above times except for the pre-infusion state was 1.10 +/-0.13, 1.86 +/-0.21, 1.80 +/-0.30, 1.76 +/-0.27, 1.74 +/-0.20, 0.07 +/-0.02 and 0.03 +/-0.01, respectively(p<0.05). The hepatic parenchymal iron content increased rapidly from just after SPIO infusion, reaching its maximal level (as revealed by histologic specimens) at 15 minutes, sustaining this for up to 4 hours, and then decreasing gradually over periods of 24 and 96 hours. These results show that serial changes in patterns of MR spectra and the signal intensity seen on T2WI images correlate closely with changes in hepatic parenchymal iron content. CONCLUSION: Elevated hepatic parenchymal iron content leads to increases in the relative intensity of unknown peaks at around 4.0 ppm and decreases in the relative intensity of lipid peaks.

Analysis of Signal Intensity Curve on Dynamic Contrast-Enhanced MR Imaging of Postoperative Scars in Rabbits:Comparison of Gadopentetate Dimeglumine and 24-gadolinium-tetraazacy-clododecanetetraacetic acid (DOTA)-dendrimer

PURPOSE: To compare the enhancement patterns of 24-gadolinium-tetrazacyclodode-cane tetracetic acid (DOTA)-dendrimer (Gadomer-17) with those of gadopentetate dimeglumine (Magnevist) in postoperative scars in rabbits. MATERIALS AND METHODS: Twelve rabbit thighs with experimentally induced postoperative scars underwent dynamic contrast-enhanced MR imaging with both Gadomer-17 and gadopentetate dimeglumine at a 24-hr interval at one (n = 10), two (n = 8) and three months (n=4) after scar induction. The enhancement and the ratios of lesions at each time point, peak enhancement ratios, and the slope and shape of curves were assessed. RESULTS: At all time points, enhancement ratios were significantly lower after the injection of Gadomer-17 than with gadopentetate dimeglumine (p<0.05). Peak enhancement ratios were significantly lower with Gadomer-17 (1.29+/-0.15) than with gadopentetate dimeglumine (1.61+/-0.31) (p<0.01). The slope values were 2.99%/min+/-2.72 after Gadomer-17 injection and 8.99%/min+/-7.32 after gadopentetate dimeglumine injection (p<0.01). The enhancement ratio curves showed mostly the plateau pattern with Gadomer-17 (90.9%), while for gadopentetate dimeglumine, the curve pattern was either plateau (50%) or washout (50%). Difference in enhancement characteristics between the two contrast agents were most pronounced for one-month scars. CONCLUSION: With Gadomer-17, weaker enhancement and the plateau pattern were found in postoperative scars, whereas stronger enhancement and either washout or the plateau pattern were found with gadopentetate dimeglumine.

MR Findings of Bowel Ischemia with Mesenteric Vascular Occlusion: Comparison with Pathologic Findings in a Cat Model

PURPOSE: In order to determine the characteristic MR findings for the early diagnosis of bowel ischemia, we analysed the dynamic enhanced MR images of ischemic bowel induced by mesenteric vascular occlusion in a cat model, and compared the T1-and T2- weighted images (WI) of extracted bowel with the pathologic findings. MATERIALS AND METHODS: According to the ischemic period, twelve cats were assigned to either the normal control group (no ischemic period, n=2), the acute ischemic group (ligation of mesenteric vessels for 3 hours, n=6) or the subacute ischemic group (ligation of mesenteric vessels for 10 hours, n=4). Under general anes-thesia,laparotomy was performed. The ileal artery and vein were ligated, and a columnar surface coil was ap-plied to the expected bowel ischemia. Using a 4.7 T MR scanner, contrast-enhanced T1WI were obtained, after bolus injection of contrast media, at 10, 20, 30, 60, and 90minutes. After formalin fixation of the extracted bowel, T1- and T2WI were obtained, and the specimens were pathologically examined. MR signal intensity at each layer of the bowel wall was measured and compared with the histopathologic findings. RESULTS: On contrast enhanced MR images, the submucosal layer showed most intensive enhancement, fol-lowed-in decreasing order of signal intensity- by muscle and mucosa. Time to peak enhancement of bowel wall was 10-minutes in the normal control group, and 20 and 60minutes in the acute and subacute bowel is-chemia groups, respectively. On T1WI, no significant differences in signal intensity were observed between the ischemic group and the normal control group. On T2WI, the signal intensity of the submucosal layer of the acute ischemic group was significantly higher than that of the normal control or subacute ischemic group, and the signal intensity of the muscular layer of the ischemic group was significantly higher than that of the normal control group. CONCLUSION: Time to peak enhancement of bowel wall was a helpful criterion for assessment of the ischemic period. Analysis of the signal intensity of the bowel wall layer was useful for the early detection of bowel ischemia.

MR Angiography of Stenosis and Aneurysm Models in the Pulsatile Flow: Variation with Imaging Parameters and Concentration of Contrast Media

PURPOSE: The image quality of magnetic resonance angiography (MRA) varies according to the imaging techniques applied and the parameters affected by blood flow patterns, as well as by the shape of the blood vessels. This study was designed to assess the influence on signal intensity and its distribution of the geometry of these vessels, the imaging parameters, and the concentration of contrast media in MRA of stenosis and aneurysm models. MATERIALS AND METHODS: MRA was performed in stenosis and aneurysm models made of glass tubes, using pulsatile flow with viscosity and flow profile similar to those of blood. Slice and maximum intensity projection (MIP) images were obtained using various imaging techniques and parameters ; there was variation in repetition time, flip angle, imaging planes, and concentrations of contrast media. On slice images of three-dimensional (3D) time-of-flight (TOF) techniques, flow signal intensity was measured at five locations in the models, and contrast ratio was calculated as the difference between flow signal intensity (SI) and background signal intensity (SIb) divided by background signal intensity or (SI-SIb)/SIb. MIP images obtained by various techniques and using various parameters were also analyzed, with emphasis in the stenosis model on demonstrated degree of stenosis, severity of signal void and image distortion, and in the aneurysm model, on degree of visualization, distortion of contour and distribution of signals. RESULTS: In 3D TOF, the shortest TR (36 msec) and the largest FA (50 degree) resulted in the highest contrast ratio, but larger flip angles did not effectively demonstrate the demonstration of the peripheral part of the aneurysm . Loss of signal was most prominent in images of the stenosis model obtained with parallel or oblique planes to the flow direction. The two-dimensional TOF technique also caused signal void in stenosis, but precisely demonstrated the aneurysm, with dense opacification of the peripheral part. The phase contrast technique showed some distortions in the imaging of stenosis, and partial opacification of ananeurysm. Contrast enhanced imaging offered no advantages in the imaging of the stenosis, but was excellent for demonstration of the aneurysm. CONCLUSION: This study demonstrates a spectrum of MRA images of stenosis and aneurysm model according to variation in imaging parameters and the concentration of contrast media.