Materials and Methods: All experiments were approved by the Institutional Animal Care and Use Committee. Phantom studies were performed to quantify microsphere relaxivity and volume susceptibility properties and compare image contrast patterns resulting from aggregate deposition of unlabeled and iron-labeled microspheres. In seven rabbits in which nine VX2 liver tumors were implanted, T2*-weighted gradient-echo (GRE) MR images with negative image contrast (NC), white-marker (WM) GRE images with positive image contrast (PC), and on-resonance water-suppression turbo spin-echo (SE) images with PC were obtained before and after catheter-directed administration of microspheres into the hepatic artery. During each injection, serial GRE acquisitions were performed for real-time visualization of microsphere delivery. Contrast-to-noise ratios (CNRs) were measured between regions of microsphere accumulation and regions of normal liver parenchyma that demonstrated no apparent microsphere accumulation. Pre- and postinjection CNR measurements at identical spatial positions were compared by using paired t test ( = .05).
Results: Conventional microspheres did not produce detectable image contrast in phantoms. Iron-labeled microspheres produced susceptibility-induced dipole patterns with spatial extent of image contrast increasing with increasing microsphere dose. Real-time image series depicted both preferential delivery to tumor tissues and nontargeted delivery to adjacent organs. T2*-weighted GRE, WM GRE, and on-resonance water-suppression turbo SE each permitted in vivo visualization of the microsphere deposition, with postinjection CNR values (mean, 14.29 ± 3.98 [standard deviation], 1.87 ± 0.93, and 19.30 ± 8.72, respectively) significantly greater than corresponding preinjection CNR values (mean, 2.02 ± 4.65, 0.02 ± 0.27, 0.85 ± 2.65, respectively) (P < .05).
Conclusion: Microsphere tracking during radioembolization may permit real-time verification of delivery and detection of extrahepatic shunting.
© RSNA, 2008
]]>Materials and Methods: The handling methods used for all the animals in this study were approved by the institutional committee for animal experiments. Diffusion-tensor MR imaging was performed in four healthy common marmosets, and in two of these animals, manganese-enhanced MR imaging tract tracing was performed by using a 7.0-T MR imaging unit. The visual pathways were quantitatively investigated in terms of the manganese distribution observed on the manganese-enhanced MR images. The images obtained with DTT and manganese-enhanced MR imaging tract tracing were qualitatively compared, and the features of the visual pathway were verified through fusion of the reconstructed images obtained by using these two modalities.
Results: DTT provided information regarding the neuroanatomic features of the marmoset visual pathway and revealed the bilateral branching patterns of the typical primate retinogeniculate pathways, although several incorrectly tracked fibers were noted. The distribution of manganese on the manganese-enhanced MR images revealed bilateral innervation of the retinal projections and depicted the layered internal structure of the lateral geniculate nuclei bilaterally, depending on the ocularity of each layer. These morphologic findings were consistent with those of previous histopathologic studies.
Conclusion: The findings of this preliminary study raise the possibility that DTT is useful for visualizing the neuronal fiber trajectories in primate visual pathways.
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© RSNA, 2008
]]>Materials and Methods: Experiments were approved by the institutional animal care committee. Eleven rabbits were imaged at baseline before injection of a contrast agent and then serially 5–30 minutes, 2 hours, 1 day, and 3 days after a single intravenous bolus injection of 80 µmol of MION-47 per kilogram of body weight (n = 6) or 250 µmol/kg MION-47 (n = 5). Conventional T1-weighted MR angiography and IRON MR angiography were performed on a clinical 3.0-T imager. Signal-to-noise and contrast-to-noise ratios were measured in the aorta of rabbits in vivo. Venous blood was obtained from the rabbits before and after MION-47 injection for use in phantom studies.
Results: In vitro blood that contained MION-47 appeared signal attenuated on T1-weighted angiograms, while characteristic signal-enhanced dipolar fields were observed on IRON angiograms. In vivo, the vessel lumen was signal attenuated on T1-weighted MR angiograms after MION-47 injection, while IRON supported high intravascular contrast by simultaneously providing positive signal within the vessels and suppressing background tissue (mean contrast-to-noise ratio, 61.9 ± 12.4 [standard deviation] after injection vs 1.1 ± 0.4 at baseline, P < .001). Contrast-to-noise ratio was higher on IRON MR angiograms than on conventional T1-weighted MR angiograms (9.0 ± 2.5, P < .001 vs IRON MR angiography) and persisted up to 24 hours after MION-47 injection (76.2 ± 15.9, P < .001 vs baseline).
Conclusion: IRON MR angiography in conjunction with superparamagnetic nanoparticle administration provides high intravascular contrast over a long time and without the need for image subtraction.
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© RSNA, 2008
]]>Materials and Methods: The institutional animal care and use committee approved this study. Pigs underwent coronary artery occlusion and reperfusion and served as either control (n = 8) or VM202-treated (n = 8) animals. VM202 was transferred intramyocardially into four infarcted and four periinfarcted sites. Cardiac magnetic resonance (MR) imaging (cine, perfusion, delayed enhancement) was performed in acute (3 days) and chronic (50 days ± 3 [standard error of the mean]) infarction. Histopathologic findings were used to characterize and quantify neovascularization. The t test was utilized to compare treated and control groups and to assess changes over time.
Results: In acute infarction, MR imaging estimates of function, perfusion, and viability showed no difference between the groups. In chronic infarction, however, VM202 increased maximum signal intensity and upslope at first-pass perfusion imaging and reduced infarct size at perfusion and delayed-enhancement imaging. These changes were associated with a decrease in end-diastolic (2.15 mL/kg ± 0.12 to 1.73 mL/kg ± 0.10, P < .01) and end-systolic (1.33 mL/kg ± 0.07 to 0.92 mL/kg ± 0.08, P < .001) volumes and an increase in ejection fraction (38.2% ± 1.3 to 47.0% ± 1.8, P < .001). In contrast, LV function deteriorated further in control animals. Compared with control animals, VM202-treated animals revealed peninsulas and/or islands of viable myocardium in infarcted and periinfarcted regions and greater number of capillaries (218 per square millimeter ± 19 vs 119 per square millimeter ± 17, P < .05) and arterioles (21 per square millimeter ± 4 vs 3 per square millimeter ± 1, P < .001).
Conclusion: Intramyocardial transfer of VM202 improved myocardial perfusion, viability, and LV function.
© RSNA, 2008
]]>Materials and Methods: Four atherosclerotic specimens were examined with 64-section dual-energy multidetector CT by using a novel dual-detector "double-decker" design, with stacked high- and low-energy detector arrays with 32 x 0.625-mm collimation, at 140 kVp and 400 mAs, acquiring simultaneous and isopedic low- and high-energy data sets. Additionally, combined-energy data sets were calculated, and an enhancement algorithm was proposed. Cardiac motion was simulated by an anthropomorphically moving phantom, and OCT was used as a reference standard for plaque quantification. Univariate general linear model (GLM) analysis was used to compare sizes of plaque calcifications determined with OCT with those determined with dual-energy multidetector CT, and the significance of factors such as cardiac motion was assessed.
Results: GLM analysis revealed that plaque quantification based on low-, high-, and combined-energy data sets differed significantly from that based on OCT (P < .001). Greater data variation occurred in smaller (<8 mm2) and larger (>12 mm2) calcifications. Comparison of calcified plaque sizes determined with OCT with those determined with the dual-energy multidetector CT enhancement algorithm revealed no significant difference (P = .550). Cardiac activity led to a slight increase in data variation in regard to OCT for corresponding static (mean, 10.2% ± 3.2 [standard deviation]) and dynamic (13.8% ± 4.9) dual-energy multidetector CT data sets.
Conclusion: Dual-energy multidetector CT with novel postprocessing techniques enhanced accuracy of calcified plaque quantification by reducing effects of tissue blooming and beam hardening beyond single-energy multidetector CT.
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© RSNA, 2008
]]>Materials and Methods: This study, which had Animal Care and Use Committee approval, was performed in healthy, growing swine (weight range, 40–45 kg; n = 10). GACE was performed in five swine with the infusion of sodium morrhuate (125 µg) selectively into the gastric arteries that supply the fundus. Five control animals underwent a sham procedure with 5 mL of saline. Weight and fasting plasma ghrelin levels were obtained in animals at baseline and in weeks 1–4. Statistical testing for substantial differences in ghrelin blood levels over time and between treated and untreated animals was performed by using a cross-sectional time-series linear model with feasibility generalized least squares.
Results: The pattern of the change in ghrelin levels over time was significantly different between control and treated animals (P < .004). In treated animals, ghrelin levels were significantly reduced at week 1 (mean, 664.1 pg/mL ± 103.1 [standard error of the mean], P < .02), week 2 (mean, 618.1 pg/mL ± 180.4, P < .001), week 3 (mean, 578.4 pg/mL ± 214.9, P < .001), and week 4 (mean, 876.6 pg/mL ± 228.6, P < .03) relative to baseline (mean, 1006.3 pg/mL ± 190.1). The percentage change in serum ghrelin values in swine treated with GACE decreased from baseline to –34%, –38.6%, –42.5%, and –12.9% during weeks 1–4, respectively. In control swine, percentage change in serum ghrelin was –1.7%, –9.7%, +2.6%, and +18.2% during weeks 1–4, respectively. At the end of 4 weeks, control swine continued to gain weight, with a 15.1% increase from their original weight, while the weight in swine treated with GACE plateaued at an increase of 7.8% from the original weight.
Conclusion: Catheter-directed GACE can suppress the appetite hormone ghrelin and affect weight gain.
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© RSNA, 2008
]]>Materials and Methods: Human subject studies were institutional review board approved and HIPAA compliant; informed consent was obtained. Cortical BW concentration was determined with custom-designed MR imaging sequences at 3.0 T and was validated in sheep and human cortical bone by using exchange of native water with deuterium oxide (D2O). The submillisecond T2* of BW requires correction for relaxation losses during the radiofrequency pulse. BW was measured at the tibial midshaft in healthy pre- and postmenopausal women (mean age, 34.6 and 69.4 years, respectively; n = 5 in each group) and in patients receiving maintenance hemodialysis (mean age, 51.8 years; n = 6) and was compared with bone mineral density (BMD) at the same site at peripheral quantitative computed tomography, as well as with BMD of the lumbar spine and hip at dual x-ray absorptiometry. Data were analyzed by using the Pearson correlation coefficient and two-sided t tests as appropriate.
Results: Excellent agreement was obtained ex vivo between the water displaced by using D2O exchange and water measured with respect to a reference sample (r2 = 0.99, P < .001). In vivo, BW in the postmenopausal group was greater by 65% (28.7% ± 1.3 [standard deviation] vs 17.4% ± 2.2, P < .001) than in the premenopausal group, and patients with renal osteodystrophy had higher BW (41.4% ± 9.6) than the premenopausal group by 135% (P < .001) and the postmenopausal group by 43% (P = .02). BMD showed an opposite behavior, with much smaller group differences. Because the majority of BW is in the pore system of cortical bone, this parameter provides a surrogate measure for cortical porosity.
Conclusion: A new MR imaging–based method for quantifying BW noninvasively has been demonstrated.
© RSNA, 2008
]]>Materials and Methods: The Basel Veterinary Authority approved this experiment. Actively sensitized female Balb/c mice received ovalbumin or saline and underwent MR imaging (a) once 24 hours after the fourth administration of ovalbumin or saline (n = 25) or (b) several times between and after ovalbumin or saline administrations (n = 22) to determine the volume of fluid signal induced by an allergen. Images were acquired in spontaneously breathing animals, without cardiac or respiratory gating. Signal detected with a gradient-echo sequence was compared with bronchoalveolar lavage (BAL) fluid parameters and with perivascular and peribronchial edema and mucus observed at histologic analysis.
Results: Up to 24 hours after the fourth administration of ovalbumin, intense and continuous fluid signals (volume, 40–50 µL) were detected in proximal lung regions. At 72 hours after the fourth administration of ovalbumin, remaining signals (21.1 µL ± 3.8) had a discontinuous texture. The number of eosinophils in the BAL fluid at 24 and 72 hours and their activation were higher in mice that received ovalbumin than in those that received saline. Histologic analysis revealed edema and secreted mucus in the early phase, whereas only mucus was encountered in the late phase.
Conclusion: These findings suggest that the main component of the early response was plasma leakage (edema), while the main component of the late response was secreted mucus. With the technique validated, the basis for pharmacologic studies in this murine model of lung inflammation with use of MR imaging as a noninvasive readout was provided.
© RSNA, 2008
]]>Materials and Methods: Animal experiments had institutional animal care and use committee approval. Four groups of nude mice bearing luciferase-positive breast tumors (four to five mice with eight to 10 tumors per group) were injected intravenously with 0 mg (group 1), 0.025 mg (group 2), 0.100 mg (group 3), or 0.200 mg (group 4) of TRA-8 on days 0 and 3. Diffusion-weighted imaging, anatomic MR imaging, and bioluminescence imaging were performed on days 0, 3, and 6 before dosing. Averaged apparent diffusion coefficients (ADCs) for both whole tumor volume and a 1-mm peripheral tumor shell were calculated and were compared with tumor volume and living tumor cell changes. After imaging at day 6, proliferating and apoptotic cell densities were measured with Ki67 and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling, or TUNEL, staining, respectively, and were compared with cleaved caspase-3 density.
Results: The ADC increase at day 3 was dependent on TRA-8 dose level, averaging 6% ± 3 (standard error of mean), 19% ± 4, 14% ± 4, and 34% ± 7 in the whole tumor volume and 1% ± 2, 9% ± 5, 13% ± 5, and 30% ± 8 in the outer 1-mm tumor shell only for groups 1, 2, 3, and 4, respectively. The ADC increase in group 4 was significantly higher (P = .0008 and P = .0189 for whole tumor volume and peripheral region, respectively) than that in group 1 on day 3, whereas tumor size did not significantly differ. At day 3, the dose-dependent ADC increases were linearly proportional to apoptotic cell and cleaved caspase-3 densities and were inversely proportional to the density of cells showing Ki67 expression.
Conclusion: Diffusion-weighted imaging enabled measurement of early breast tumor response to TRA-8 treatment, prior to detectable tumor shrinkage, providing an effective mechanism to noninvasively monitor TRA-8 efficacy.
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© RSNA, 2008
]]>Materials and Methods: After local ethics committee approval and written informed consent were obtained, five patients (two women, three men; mean age, 64.4 years; age range, 45–76 years) scheduled for computed tomography (CT) and 20 patients (six women, 14 men; mean age, 68.5 years; age range, 53–85 years) scheduled for PTA of lower limb arteries were prospectively entered into the study. Blood samples were taken before the first exposure to ionizing radiation and 5 minutes, 1 hour, 6 hours, and 24 hours after the last exposure. Additional samples were taken from the irradiated limb (femoral vein) of three patients who underwent PTA—before the first radiation exposure, 5 and 10 minutes after the first exposure, and 5 minutes after the last exposure. Lymphocytes were isolated, fixed, and stained with anti-H2AX antibody, and H2AX focus yields were determined with fluorescence microscopy. Data were analyzed with linear regression and two-sample F tests.
Results: Mean increase in number of H2AX foci after CT (7.78 per 1 Gy · cm) depended linearly on dose-length product (r = 0.997). Number of foci reached background levels within 24 hours. Mean numbers of H2AX foci per cell increased by factors of 4.08–20.67 in blood samples taken 5 minutes after PTA compared with mean numbers of foci before PTA. Mean radiation dose increase, 6.56/(10 Gy · cm2), depended linearly on dose-area product (r = 0.993). Maximal focus yield in cells taken directly from the irradiated limb was higher than that in cells from the systemic circulation (by mean factor of 1.46). Data showed compromised DSB repair capacity after PTA (P < .05). Mean number of foci at 24 hours (0.07 focus per cell) was significantly higher than mean number of foci in cell background (0.04 focus per cell, P < .05).
Conclusion: H2AX focus formation can be used to determine in vivo induction of DNA DSBs after PTA. DSB repair capacity is compromised in patients who undergo PTA of lower limb arteries.
© RSNA, 2008
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