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Objectives: This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]).Background: The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility.Methods: Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days.Results: After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis.Conclusions: Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques. [ABSTRACT FROM AUTHOR]

Background: Interventional magnetic resonance imaging (MRI) at 3T benefits from higher spatial and temporal resolution, but artifacts of metallic instruments are often larger and may obscure target structures., Purpose: To test that compressed sensing (CS) slice-encoding metal artifact correction (SEMAC) is feasible for 3T interventional MRI and affords more accurate instrument visualization than turbo spin echo (TSE) and gradient echo (GRE) techniques, and facilitates faster data acquisition than conventional SEMAC., Study Type: Prospective., Phantom and Subjects: Cadaveric animal and 20 human subjects., Field Strength/sequence: TSE (acquisition time 31 sec), GRE (28-33 sec), SEMAC (128 sec), and CS-SEMAC (57 sec) pulse sequences were evaluated at 3T., Assessment: Artifact width and length, signal-to-noise (SNR), and contrast-to-noise (CNR) ratios of 14-22G MR-conditional needles were measured in a phantom. Subsequently, high-bandwidth TSE and CS-SEMAC sequences were assessed in vivo with 20 patient procedures for the size of the metal artifact, image sharpness, image noise, motion artifacts, image contrast, and target, instrument, and structural visibility., Statistical Tests: Repeated-measures-analysis-of-variances and Mann-Whitney U-tests were applied. P ≤ 0.05 was considered statistically significant., Results: CS-SEMAC and SEMAC created the smallest needle artifact widths (3.2-3.3 ± 0.4 mm, P = 1.0), whereas GRE showed the largest needle artifact widths (8.5-8.6 ± 0.4 mm) (P < 0.001). The artifact width difference between high-bandwidth TSE and CS-SEMAC was 0.8 ± 0.6 mm (P < 0.01). SEMAC and CS-SEMAC created the lowest average needle tip errors (0.3-0.4 ± 0.1 mm, P = 1.0). The average tip error difference between high-bandwidth TSE and SEMAC/CS-SEMAC was 2.0 ± 1.7 mm (P < 0.01). SNR and CNR were similar on TSE, SEMAC, and CS-SEMAC, and lowest on GRE. CS-SEMAC yielded smaller artifacts, less noise, less motion, and better instrument visibility (P < 0.001); high-bandwidth TSE showed better sharpness (P < 0.001) and targets visibility (P = 0.007); whereas image contrast (P = 0.273) and structural visibility (P = 0.1) were similar., Data Conclusion: CS-SEMAC is feasible for interventional MRI at 3T, visualizes instruments with higher accuracy than high-bandwidth TSE and GRE, and can be acquired 55% faster than conventional SEMAC., Level of Evidence: 2 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2018;47:1306-1315., (© 2017 International Society for Magnetic Resonance in Medicine.)

Objectives: To test the hypothesis that a fourfold CAIPIRINHA accelerated, 10-min, high-resolution, isotropic 3D TSE MRI prototype protocol of the ankle derives equal or better quality than a 20-min 2D TSE standard protocol., Methods: Following internal review board approval and informed consent, 3-Tesla MRI of the ankle was obtained in 24 asymptomatic subjects including 10-min 3D CAIPIRINHA SPACE TSE prototype and 20-min 2D TSE standard protocols. Outcome variables included image quality and visibility of anatomical structures using 5-point Likert scales. Non-parametric statistical testing was used. P values ≤0.001 were considered significant., Results: Edge sharpness, contrast resolution, uniformity, noise, fat suppression and magic angle effects were without statistical difference on 2D and 3D TSE images (p > 0.035). Fluid was mildly brighter on intermediate-weighted 2D images (p < 0.001), whereas 3D images had substantially less partial volume, chemical shift and no pulsatile-flow artifacts (p < 0.001). Oblique and curved planar 3D images resulted in mildly-to-substantially improved visualization of joints, spring, bifurcate, syndesmotic, collateral and sinus tarsi ligaments, and tendons (p < 0.001, respectively)., Conclusions: 3D TSE MRI with CAIPIRINHA acceleration enables high-spatial resolution oblique and curved planar MRI of the ankle and visualization of ligaments, tendons and joints equally well or better than a more time-consuming anisotropic 2D TSE MRI., Key Points: • High-resolution 3D TSE MRI improves visualization of ankle structures. • Limitations of current 3D TSE MRI include long scan times. • 3D CAIPIRINHA SPACE allows now a fourfold-accelerated data acquisition. • 3D CAIPIRINHA SPACE enables high-spatial-resolution ankle MRI within 10 min. • 10-min 3D CAIPIRINHA SPACE produces equal-or-better quality than 20-min 2D TSE.

Purpose: To demonstrate the feasibility, safety, and effectiveness of image-guided sclerotherapy of low-flow vascular malformations using a 1.5 Tesla (T) MR scanner with real-time imaging capability and in-suite fluoroscopy., Materials and Methods: Thirty-three procedures were performed with real-time 1.5T MR-guidance on 22 patients with a vascular malformation in the neck (n = 2), chest (n = 6), abdomen and pelvis (n = 15), and extremities (n = 11). Quantitative analysis was performed for changes in (a) planning time, (b) targeting time (interval between needle skin puncture and lesion access), (c) intervention time (interval between needle skin puncture and needle removal), and (d) total procedure time. Qualitative analysis was performed for (a) success of therapy and (b) occurrence of complications., Results: Technical success was achieved in 29 of 33 procedures. The average planning time did not significantly change between the first seven procedures and the last seven procedures (P = 0.447). The average targeting time decreased by 0:24:45 (hours:minutes:seconds) (P = 0.043), the average intervention time decreased by 0:26:58 (P = 0.022), and the average procedure time decreased by 0:28:41 (P = 0.046) when comparing the first seven procedures and the last seven procedures. Overall, there was an improvement in the patients' predominant symptoms following 82% of procedures, including a significant decrease in average pain following therapy (P < 0.001). There was a minor complication rate of 3% with no major complications., Conclusion: MR-guided percutaneous sclerotherapy seems to be a safe, effective, and versatile technique for treating low-flow vascular malformations., Level of Evidence: 3 J. Magn. Reson. Imaging 2017;45:1154-1162., (© 2016 International Society for Magnetic Resonance in Medicine.)

Objective: The aim of this study was to prospectively test the hypothesis that a 2-dimensional (2D) CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) sampling pattern facilitates 5-minute high spatial resolution 3-dimensional (3D) sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) magnetic resonance imaging (MRI) of the knee with image quality similar or better than current 2D turbo spin echo (TSE) and 3D SPACE standards., Materials and Methods: The study was approved by our institutional review board. Twenty asymptomatic subjects (12 men, 8 women; mean age, 42 years; age range, 24-65 years) underwent 3 T MRI of the knee. A 4-fold accelerated 3D SPACE TSE prototype with 2D CAIPIRINHA sampling pattern and 5-minute acquisition time was compared with commercially available 2-fold and 4-fold accelerated 3D SPACE and 2D TSE pulse sequences with acquisition times of 11 minutes and 15 seconds, 6 minutes and 30 seconds, as well as 9 minutes and 48 seconds, respectively. Outcome variables included image quality, anatomic visibility, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Statistical analysis included Friedman, repeated measures analysis of variances, and Cohen's weighted κ tests. Bonferroni-corrected P values of 0.005 and less were considered statistically significant., Results: Overall, image quality, visibility of anatomic structures, SNR, and CNR of 3D CAIPIRINHA SPACE were statistically similar to 2-fold accelerated 3D SPACE and significantly better than 4-fold accelerated 3D SPACE, which exhibited degrading parallel imaging artifacts. Compared with 2.5-mm 2D TSE images, 0.5-mm 3D CAIPIRINHA SPACE images showed statistically similar good edge sharpness and very good contrast resolution, and significantly less partial volume as well as absent chemical shift and pulsatile flow artifacts. Visibility of menisci, anterior cruciate ligament, posterior cruciate ligament, medial collateral ligament, and lateral collateral ligament was good to very good on 0.5-mm 3D CAIPIRINHA SPACE images as compared with good on 2.5-mm 2D TSE image (P < 0.005). The SNR of fat, fluid, and cartilage as well as CNR between cartilage, fluid, fat, posterior cruciate ligament, and menisci were minimally higher on 2.5-mm 2D TSE image (P < 0.005). Image quality, visibility of anatomic structures, SNR, and CNR of 2.5-mm 3D CAIPIRINHA SPACE and 2.5-mm 2D TSE images were good to very good without significant differences., Conclusions: Three-dimensional SPACE with 2D CAIPIRINHA sampling pattern enables high-quality 3D TSE MRI of the knee at an acquisition time of 5 minutes and image quality, visibility of anatomic structures, SNR, and CNR similar to conventional 3D SPACE and 2D TSE, both of which require approximately 10-minute acquisition times.

Objective: The aim of this study was to prospectively test the hypothesis that a compressed sensing-based slice encoding for metal artifact correction (SEMAC) turbo spin echo (TSE) pulse sequence prototype facilitates high-resolution metal artifact reduction magnetic resonance imaging (MRI) of cobalt-chromium knee arthroplasty implants within acquisition times of less than 5 minutes, thereby yielding better image quality than high-bandwidth (BW) TSE of similar length and similar image quality than lengthier SEMAC standard of reference pulse sequences., Materials and Methods: This prospective study was approved by our institutional review board. Twenty asymptomatic subjects (12 men, 8 women; mean age, 56 years; age range, 44-82 years) with total knee arthroplasty implants underwent MRI of the knee using a commercially available, clinical 1.5 T MRI system. Two compressed sensing-accelerated SEMAC prototype pulse sequences with 8-fold undersampling and acquisition times of approximately 5 minutes each were compared with commercially available high-BW and SEMAC pulse sequences with acquisition times of approximately 5 minutes and 11 minutes, respectively. For each pulse sequence type, sagittal intermediate-weighted (TR, 3750-4120 milliseconds; TE, 26-28 milliseconds; voxel size, 0.5 × 0.5 × 3 mm) and short tau inversion recovery (TR, 4010 milliseconds; TE, 5.2-7.5 milliseconds; voxel size, 0.8 × 0.8 × 4 mm) were acquired. Outcome variables included image quality, display of the bone-implant interfaces and pertinent knee structures, artifact size, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Statistical analysis included Friedman, repeated measures analysis of variances, and Cohen weighted k tests. Bonferroni-corrected P values of 0.005 and less were considered statistically significant., Results: Image quality, bone-implant interfaces, anatomic structures, artifact size, SNR, and CNR parameters were statistically similar between the compressed sensing-accelerated SEMAC prototype and SEMAC commercial pulse sequences. There was mild blur on images of both SEMAC sequences when compared with high-BW images (P < 0.001), which however did not impair the assessment of knee structures. Metal artifact reduction and visibility of central knee structures and bone-implant interfaces were good to very good and significantly better on both types of SEMAC than on high-BW images (P < 0.004). All 3 pulse sequences showed peripheral structures similarly well. The implant artifact size was 46% to 51% larger on high-BW images when compared with both types of SEMAC images (P < 0.0001). Signal-to-noise ratios and CNRs of fat tissue, tendon tissue, muscle tissue, and fluid were statistically similar on intermediate-weighted MR images of all 3 pulse sequence types. On short tau inversion recovery images, the SNRs of tendon tissue and the CNRs of fat and fluid, fluid and muscle, as well as fluid and tendon were significantly higher on SEMAC and compressed sensing SEMAC images (P < 0.005, respectively)., Conclusions: We accept the hypothesis that prospective compressed sensing acceleration of SEMAC is feasible for high-quality metal artifact reduction MRI of cobalt-chromium knee arthroplasty implants in less than 5 minutes and yields better quality than high-BW TSE and similarly high quality than lengthier SEMAC pulse sequences.

Objective: Compressed sensing (CS) acceleration has been theorized for slice encoding for metal artifact correction (SEMAC), but has not been shown to be feasible. Therefore, we tested the hypothesis that CS-SEMAC is feasible for MRI of metal-on-metal hip resurfacing implants., Materials and Methods: Following prospective institutional review board approval, 22 subjects with metal-on-metal hip resurfacing implants underwent 1.5 T MRI. We compared CS-SEMAC prototype, high-bandwidth TSE, and SEMAC sequences with acquisition times of 4-5, 4-5 and 10-12 min, respectively. Outcome measures included bone-implant interfaces, image quality, periprosthetic structures, artifact size, and signal- and contrast-to-noise ratios (SNR and CNR). Using Friedman, repeated measures analysis of variances, and Cohen's weighted kappa tests, Bonferroni-corrected p-values of 0.005 and less were considered statistically significant., Results: There was no statistical difference of outcomes measures of SEMAC and CS-SEMAC images. Visibility of implant-bone interfaces and pseudocapsule as well as fat suppression and metal reduction were "adequate" to "good" on CS-SEMAC and "non-diagnostic" to "adequate" on high-BW TSE (p < 0.001, respectively). SEMAC and CS-SEMAC showed mild blur and ripple artifacts. The metal artifact size was 63 % larger for high-BW TSE as compared to SEMAC and CS-SEMAC (p < 0.0001, respectively). CNRs were sufficiently high and statistically similar, with the exception of CNR of fluid and muscle and CNR of fluid and tendon, which were higher on intermediate-weighted high-BW TSE (p < 0.005, respectively)., Conclusion: Compressed sensing acceleration enables the time-neutral use of SEMAC for MRI of metal-on-metal hip resurfacing implants when compared to high-BW TSE and image quality similar to conventional SEMAC.

Purpose: To assess the diagnostic value of MRI using dual-echo (2PD) and triple-echo (3PD) chemical shift imaging for liver fat quantification against multi-echo T2 corrected MR spectroscopy (MRS) used as the reference standard, and examine the effect of T2(*) imaging on accuracy of MRI for fat quantification., Materials and Methods: Patients who underwent 1.5T liver MRI that incorporated 2PD, 3PD, multi-echo T2(*) and MRS were included in this IRB approved prospective study. Regions of interest were placed in the liver to measure fat fraction (FF) with 2PD and 3PD and compared with MRS-FF. A random subset of 25 patients with a wide range of MRS-FF was analyzed with an advanced FF calculation method, to prove concordance with the 3PD. The statistical analysis included correlation stratified according to T2(*), Bland-Altman analysis, and calculation of diagnostic accuracy for detection of MRS-FF>6.25%., Results: 220 MRI studies were identified in 217 patients (mean BMI 28.0±5.6). 57/217 (26.2%) patients demonstrated liver steatosis (MRS-FF>6.25%). Bland-Altman analysis revealed strong agreement between 3PD and MRS (mean±1.96 SD: -0.5%±4.6%) and weaker agreement between 2PD and MRS (4.7%±16.0%). Sensitivity of 3PD for diagnosing FF> 6.25% was higher than that of 2PD. 3PD-FF showed minor discrepancies (coefficient of variation <10%) from FF measured with the advanced method., Conclusion: Our large series study validates the use of 3PD chemical shift sequence for detection of liver fat in the clinical environment, even in the presence of T2(*) shortening., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Image-guided treatment of low-flow vascular (venous or lymphatic) malformations presents a challenging visualization problem, regardless of the imaging modality being used for guidance. The purpose of this study was to employ a new magnetic resonance imaging (MRI) sequence, T2 -weighted interrupted balanced steady-state free precession (T2 W-iSSFP), for real-time image guidance of needle insertion., Materials and Methods: T2 W-iSSFP uses variable flip angle balanced steady-state free precession (bSSFP, a.k.a. SSFP) to establish T2 -weighting and fat suppression. Swine (n = 3) and patients (n = 4, three female, all with venous malformations) were enrolled in the assessment. T2 -weighted turbo spin echo (T2 -TSE) with spectral adiabatic inversion recovery (SPAIR), SPAIR-T2 -TSE or T2 -TSE for short, was used as the reference. T2 -weighted half Fourier acquired single shot turbo spin echo (T2 -HASTE) with SPAIR (SPAIR-T2 -HASTE, T2 -HASTE for short), fat saturated bSSFP (FS-SSFP), and T2 W-iSSFP were imaged. Numeric metrics, namely, contrast-to-noise ratio (CNR) efficiency (CNR divided by the square root of acquisition time) and local sharpness (the reciprocal of edge width), were used to assess image quality. MR-guided sclerotherapy was performed on the same patients using real-time T2 W-iSSFP to guide needle insertion., Results: Comparing the visualization of needles in the images of swine, the local sharpness (mm(-1) ) was: 0.21 ± 0.06 (T2 -HASTE), 0.48 ± 0.02 (FS-SSFP), and 0.49 ± 0.03 (T2 W-iSSFP). T2 W-iSSFP is higher than T2 -HASTE (P < 0.001). For the patient images, their CNR efficiencies were: 797 ± 66 (T2 -HASTE), 281 ± 44 (FS-SSFP), and 860 ± 29 (T2 W-iSSFP). T2 W-iSSFP is higher than FS-SSFP (P < 0.02). The frame rate of T2 W-iSSFP was 2.5-3.5 frames per second. All MR-guided sclerotherapy procedures were successful, with all needles (six punctures) placed in the targets., Conclusion: T2 W-iSSFP provides effective lesion identification and needle visualization. This new pulse sequence can be used for MR-guided sclerotherapy of low-flow vascular malformations. It may have potential use in other MR-guided procedures where heavily T2 -weighted real-time images are needed., (© 2014 Wiley Periodicals, Inc.)

Purpose: To assess intrapericardial delivery of microencapsulated, xenogeneic human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic cardiovascular disease in an immunocompetent swine model., Materials and Methods: All animal experiments were approved by the institutional animal care and use committee. Stem cell microencapsulation was performed by using a modified alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol) barium sulfate to create barium-alginate microcapsules (BaCaps) that contained hMSCs. With x-ray/MR imaging guidance, eight female pigs (approximately 25 kg) were randomized to receive either BaCaps with hMSCs, empty BaCaps, naked hMSCs, or saline by using a percutaneous subxiphoid approach and were compared with animals that received empty BaCaps (n = 1) or BaCaps with hMSCs (n = 2) by using standard fluoroscopic delivery only. MR images and C-arm computed tomographic (CT) images were acquired before injection and 1 week after delivery. Animals were sacrificed immediately or at 1 week for histopathologic validation. Cardiac function between baseline and 1 week after delivery was evaluated by using a paired Student t test., Results: hMSCs remained highly viable (94.8% ± 6) 2 days after encapsulation in vitro. With x-ray/MR imaging, successful intrapericardial access and delivery were achieved in all animals. BaCaps were visible fluoroscopically and at C-arm CT immediately and 1 week after delivery. Whereas BaCaps were free floating immediately after delivery, they consolidated into a pseudoepicardial tissue patch at 1 week, with hMSCs remaining highly viable within BaCaps; naked hMSCs were poorly retained. Follow-up imaging 1 week after x-ray/MR imaging-guided intrapericardial delivery showed no evidence of pericardial adhesion and/or effusion or adverse effect on cardiac function. In contradistinction, BaCaps delivery with x-ray fluoroscopy without x-ray/MR imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1 week., Conclusion: Intrapericardial delivery of BaCaps with hMSCs leads to high cell retention and survival. With x-ray/MR imaging guidance, intrapericardial delivery can be performed safely in the absence of preexisting pericardial effusion to provide a novel route for cardiac cellular regenerative therapy.

Purpose: A prototype wireless guidance device using single sideband amplitude modulation (SSB) is presented for a 1.5T magnetic resonance imaging system., Methods: The device contained three fiducial markers each mounted to an independent receiver coil equipped with wireless SSB technology. Acquiring orthogonal projections of these markers determined the position and orientation of the device, which was used to define the scan plane for a subsequent image acquisition. Device localization and scan plane update required approximately 30 ms, so it could be interleaved with high temporal resolution imaging. Since the wireless device is used for localization and does not require full imaging capability, the design of the SSB wireless system was simplified by allowing an asynchronous clock between the transmitter and receiver., Results: When coupled to a high readout bandwidth, the error caused by the lack of a shared frequency reference was quantified to be less than one pixel (0.78 mm) in the projection acquisitions. Image guidance with the prototype was demonstrated with a phantom where a needle was successfully guided to a target and contrast was delivered., Conclusion: The feasibility of active tracking with a wireless detector array is demonstrated. Wireless arrays could be incorporated into devices to assist in image-guided procedures., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To develop and evaluate software-based methods for improving the workflow of magnetic resonance (MR)-guided percutaneous interventions., Materials and Methods: A set of methods was developed that allows the user to: 1) plan an entire procedure, 2) directly apply this plan to skin entry site localization without further imaging, and 3) place a needle under real-time MR guidance with automatic alignment of three orthogonal slices along a planned trajectory with preference to the principal patient axes. To validate targeting accuracy and time, phantom experiments (96 targets) and in vivo paraspinal and kidney needle punctures in two pigs (55 targets) were performed. The influence of trajectory obliquity, level of experience, and organ motion on targeting accuracy and time was analyzed., Results: Mean targeting error was 1.8 ± 0.9 mm (in vitro) and 2.9 ± 1.0 mm (in vivo) in all directions. No statistically significant differences in targeting accuracy between single- and double-oblique trajectories, novice and expert users, or paraspinal and kidney punctures were observed. The average time (in vivo) from trajectory planning to verification of accurate needle placement was 6 minutes., Conclusion: The developed methods allow for accurate needle placement along complex trajectories and are anticipated to reduce table time for MR-guided percutaneous needle interventions., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To evaluate and compare the technical accuracy and feasibility of magnetic resonance (MR) imaging-enhanced fluoroscopic guidance and real-time MR imaging guidance for percutaneous puncture procedures in phantoms and animals., Materials and Methods: The experimental protocol was approved by the institutional animal care and use committee. Punctures were performed in phantoms, aiming for markers (20 each for MR imaging-enhanced fluoroscopic guidance and real-time MR imaging guidance), and pigs, aiming for anatomic landmarks (10 for MR imaging-enhanced fluoroscopic guidance and five for MR imaging guidance). To guide the punctures, T1-weighted three-dimensional (3D) MR images of the phantom or pig were acquired. Additional axial and coronal T2-weighted images were used to visualize the anatomy in the animals. For MR imaging-enhanced fluoroscopic guidance, phantoms and pigs were transferred to the fluoroscopic system after initial MR imaging and C-arm computed tomography (CT) was performed. C-arm CT and MR imaging data sets were coregistered. Prototype navigation software was used to plan a puncture path with use of MR images and to superimpose it on fluoroscopic images. For real-time MR imaging, an interventional MR imaging prototype for interactive real-time section position navigation was used. Punctures were performed within the magnet bore. After completion, 3D MR imaging was performed to evaluate the accuracy of insertions. Puncture durations were compared by using the log-rank test. The Mann-Whitney U test was applied to compare the spatial errors., Results: In phantoms, the mean total error was 8.6 mm ± 2.8 with MR imaging-enhanced fluoroscopic guidance and 4.0 mm ± 1.2 with real-time MR imaging guidance (P < .001). The mean puncture time was 2 minutes 10 seconds ± 44 seconds with MR imaging-enhanced fluoroscopic guidance and 37 seconds ± 14 with real-time MR imaging guidance (P < .001). In the animal study, a tolerable distance (<1 cm) between target and needle tip was observed for both MR imaging-enhanced fluoroscopic guidance and real-time MR imaging guidance. The mean total error was 7.7 mm ± 2.4 with MR imaging-enhanced fluoroscopic guidance and 7.9 mm ± 4.9 with real-time MR imaging guidance (P = .77). The mean puncture time was 5 minutes 43 seconds ± 2 minutes 7 seconds with MR imaging-enhanced fluoroscopic guidance and 5 minutes 14 seconds ± 2 minutes 25 seconds with real-time MR imaging guidance (P = .68)., Conclusion: Both MR imaging-enhanced fluoroscopic guidance and real-time MR imaging guidance demonstrated reasonable and similar accuracy in guiding needle placement to selected targets in phantoms and animals.

Objective: Normative apparent diffusion coefficient (ADC) and fractional anisotropy (FA) metrics of the brain have been published previously. However, no larger studies evaluated the normal evolution of ADC/FA metrics of the maturing paediatric spinal cord. Goal of this study is to evaluate the age-dependent evolution of the ADC/FA values of the developing/maturing normal cervical spinal cord (CSC)., Patients and Methods: Forty-one subjects, aged less than 18 years with a negative spinal MRI study and no systemic central nervous disease, underwent diffusion tensor imaging (DTI) of the CSC. DTI metrics were measured in the centre of the CSC. Regression and ANCOVA analyses were performed to evaluate the association between ADC/FA values and age and its potential modification by sex., Results: A linear model emerged as the best fit for our data. ADC showed a continuous decrease with age; FA showed a continuous increase with age., Conclusion: The simultaneous age-related ADC decrease and FA increase likely reflect progressive maturation, myelination and fibre packing within the CSC similar to that observed in the brain. Collection of age-dependent normative DTI metrics may be helpful in the early identification and quantification of altered water diffusion in a variety of pathologies affecting the developing paediatric spinal cord., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow-derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC-Xcaps). In vitro MSC-Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x-ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC-Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast-to-noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC-Xcap-treated animals versus empty Xcaps. Post-mortem immunohistopathology of vessel density by anti-CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap-MSC-treated animals versus empty Xcaps. MSC-Xcaps represent the first x-ray-visible cellular therapeutic with enhanced efficacy for PAD treatment., (Copyright © 2012 AlphaMed Press.)

Understanding how individual cells behave inside living systems will help enable new diagnostic tools and cellular therapies. Superparamagnetic iron oxide particles can be used to label cells and theranostic capsules for noninvasive tracking using MRI. Contrast changes from superparamagnetic iron oxide are often subtle relative to intrinsic sources of contrast, presenting a detection challenge. Here, we describe a versatile postprocessing method, called Phase map cross-correlation Detection and Quantification (PDQ), that automatically identifies localized deposits of superparamagnetic iron oxide, estimating their volume magnetic susceptibility and magnetic moment. To demonstrate applicability, PDQ was used to detect and characterize superparamagnetic iron oxide-labeled magnetocapsules implanted in porcine liver and suspended in agarose gel. PDQ was also applied to mouse brains infiltrated by MPIO-labeled macrophages following traumatic brain injury; longitudinal, in vivo studies tracked individual MPIO clusters over 3 days, and tracked clusters were corroborated in ex vivo brain scans. Additionally, we applied PDQ to rat hearts infiltrated by MPIO-labeled macrophages in a transplant model of organ rejection. PDQ magnetic measurements were signal-to-noise ratio invariant for images with signal-to-noise ratio > 11. PDQ can be used with conventional gradient-echo pulse sequences, requiring no extra scan time. The method is useful for visualizing biodistribution of cells and theranostic magnetocapsules and for measuring their relative iron content., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: The authors previously developed magnetic resonance (MR)-trackable magnetocapsules (MCs) that can simultaneously immunoprotect human islet cells and noninvasively monitor portal delivery and engraftment in real time with MR imaging. This study was designed to assess the physiologic effects of the delivery of a clinical dose of MCs (140,000 capsules) into the portal vein (PV) in swine over a 1-month period., Materials and Methods: MCs were formed by using clinical-grade alginate mixed with a clinically applicable dosage of ferumoxide. Percutaneous access into the PV was obtained by using a custom-built, MR-trackable needle, and 140,000 MCs were delivered under MR guidance in five swine. Portal pressures and liver function data were obtained over a 4-week period., Results: A transient increase in portal pressure occurred immediately after MC delivery that returned to normal levels by 4 weeks after MC delivery. Liver function test results were normal during the entire period, and the appearance of the MCs on MR imaging did not change., Conclusions: A clinically applicable dose of 140,000 MCs has no adverse effects on portal pressures or liver function in this normal swine model during the first month after delivery., (Copyright © 2011 SIR. Published by Elsevier Inc. All rights reserved.)

In vivo imaging of engraftment and immunorejection of transplanted islets is critical for further clinical development, with (1)H MR imaging of superparamagnetic iron oxide-labeled cells being the current premier modality. Using perfluorocarbon nanoparticles, we present here a strategy for non-invasive imaging of cells using other modalities. To this end, human cadaveric islets were labeled with rhodamine-perfluorooctylbromide (PFOB) nanoparticles, rhodamine-perfluoropolyether (PFPE) nanoparticles or Feridex as control and tested in vitro for cell viability and c-peptide secretion for 1 week. (19)F MRI, computed tomography (CT) and ultrasound (US) imaging was performed on labeled cell phantoms and on cells following transplantation beneath the kidney capsule of mice and rabbits. PFOB and PFPE-labeling did not reduce human islet viability or glucose responsiveness as compared with unlabeled cells or SPIO-labeled cells. PFOB- and PFPE-labeled islets were effectively fluorinated for visualization by (19)F MRI. PFOB-labeled islets were acoustically reflective for detection by US imaging and became sufficiently brominated to become radiopaque allowing visualization with CT. Thus, perfluorocarbon nanoparticles are multimodal cellular contrast agents that may find applications in real-time targeted delivery and imaging of transplanted human islets or other cells in a clinically applicable manner using MRI, US or CT imaging., (Copyright © 2011 John Wiley & Sons, Ltd.)

Cell therapy continues to be an active area of basic science research with early promise in the treatment of cardiovascular diseases. However, there are many unknowns including the mechanisms by which they work, the most useful cell types, the most efficient delivery strategies, and their safety. Noninvasive imaging provides a wide array of tools to quantitatively address many of these unknowns. This article reviews echocardiography, magnetic resonance imaging, computed tomography, positron emission tomography and single photon emission tomography in the context of imaging cellular therapeutics to demonstrate how these modalities are being used to answer some of these questions.

Purpose: To evaluate the utility of inversion recovery with on-resonant water suppression (IRON) in combination with injection of the long-circulating monocrystalline iron oxide nanoparticle (MION)-47 for contrast material-enhanced magnetic resonance (MR) angiography., 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 micromol of MION-47 per kilogram of body weight (n = 6) or 250 micromol/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., ((c) RSNA, 2008.)

Purpose: To investigate the utility of inversion recovery with ON-resonant water suppression (IRON) to create positive signal in normal lymph nodes after injection of superparamagnetic nanoparticles., Materials and Methods: Experiments were conducted on six rabbits, which received a single bolus injection of 80 mumol Fe/kg monocrystalline iron oxide nanoparticle (MION-47). Magnetic resonance imaging (MRI) was performed at baseline, 1 day, and 3 days after MION-47 injection using conventional T(1)- and T(2)*-weighted sequences and IRON. Contrast-to-noise ratios (CNR) were measured in blood and in paraaortic lymph nodes., Results: On T(2)*-weighted images, as expected, signal attenuation was observed in areas of paraaortic lymph nodes after MION-47 injection. However, using IRON the paraaortic lymph nodes exhibited very high contrast enhancement, which remained 3 days after injection. CNR with IRON was 2.2 +/- 0.8 at baseline, increased markedly 1 day after injection (23.5 +/- 5.4, P < 0.01 vs. baseline), and remained high after 3 days (21.8 +/- 5.7, *P < 0.01 vs. baseline). CNR was also high in blood 1 day after injection (42.7 +/- 7.2 vs. 1.8 +/- 0.7 at baseline, P < 0.01) but approached baseline after 3 days (1.9 +/- 1.4, P = NS vs. baseline)., Conclusion: IRON in conjunction with superparamagnetic nanoparticles can be used to perform 'positive contrast' MR-lymphography, particularly 3 days after injection of the contrast agent, when signal is no longer visible within blood vessels. The proposed method may have potential as an adjunct for nodal staging in cancer screening., ((c) 2008 Wiley-Liss, Inc.)

With the recent advances in magnetic resonance (MR) labeling of cellular therapeutics, it is natural that interventional MRI techniques for targeting would be developed. This review provides an overview of the current methods of stem cell labeling and the challenges that are created with respect to interventional MRI administration. In particular, stem cell therapies will require specialized, MR-compatible devices as well as integration of graphical user interfaces with pulse sequences designed for interactive, real-time delivery in many organs. Specific applications that are being developed will be reviewed as well as strategies for future translation to the clinical realm., ((Copyright) 2008 Wiley-Liss, Inc.)

Purpose: To prospectively compare various parameters of vessels imaged at 3 T by using time-of-flight (TOF) and T2-prepared magnetic resonance (MR) angiography in a rabbit model of hind limb ischemia., Materials and Methods: Experiments were approved by the institutional animal care and use committee. Endovascular occlusion of the left superficial femoral artery was induced in 14 New Zealand white rabbits. After 2 weeks, MR angiography and conventional (x-ray) angiography were performed. Vessel sharpness was evaluated visually in the ischemic and nonischemic limbs, and the presence of small collateral vessels was evaluated in the ischemic limbs. Vessel sharpness was also quantified by evaluating the magnitude of signal intensity change at the vessel borders., Results: The sharpness of vessels in the nonischemic limbs was similar between the TOF and the T2-prepared images. In the ischemic limbs, however, T2-prepared imaging, as compared with TOF imaging, generated higher vessel sharpness in arteries with diminished blood flow (mean vessel sharpness: 44% vs 30% for popliteal arteries, 45% vs 28% for saphenous arteries; P < .001 for both comparisons) and enabled better detection of small collateral vessels (93% vs 36% of vessels, P < .001)., Conclusion: T2-prepared imaging can facilitate high-spatial-resolution MR angiography of small vessels with low blood flow and thus has potential as a tool for noninvasive evaluation of arteriogenic therapies, without use of contrast material., Supplemental Material: http://radiology.rsnajnls.org/cgi/content/full/2452062067/DC1., ((c) RSNA, 2007.)

In proton magnetic resonance imaging (MRI) metallic substances lead to magnetic field distortions that often result in signal voids in the adjacent anatomic structures. Thus, metallic objects and superparamagnetic iron oxide (SPIO)-labeled cells appear as hypointense artifacts that obscure the underlying anatomy. The ability to illuminate these structures with positive contrast would enhance noninvasive MR tracking of cellular therapeutics. Therefore, an MRI methodology that selectively highlights areas of metallic objects has been developed. Inversion-recovery with ON-resonant water suppression (IRON) employs inversion of the magnetization in conjunction with a spectrally-selective on-resonant saturation prepulse. If imaging is performed after these prepulses, positive signal is obtained from off-resonant protons in close proximity to the metallic objects. The first successful use of IRON to produce positive contrast in areas of metallic spheres and SPIO-labeled stem cells in vitro and in vivo is presented., (Copyright 2007 Wiley-Liss, Inc.)

Objectives: We sought to determine the effect of inducible nitric oxide synthase (iNOS) expression on regional contractile function and left ventricular (LV) remodeling after reperfused myocardial infarction (MI)., Background: Inducible nitric oxide synthase is known to contribute to global LV dysfunction after a large MI, but the mechanisms underlying this dysfunction remain unclear., Methods: We used immunohistochemistry to investigate the distribution of iNOS expression in wild-type (WT) and iNOS knockout (KO) mice early (day 1) and late (day 28) after reperfused MI. We also used serial cardiac magnetic resonance imaging at baseline and at 1, 7, and 28 days after MI to assess LV volumes, ejection fraction (EF), regional circumferential strain (E(cc)), and day 1 infarct size., Results: At baseline, LV volumes and EF were similar between groups. Day 1 infarct size was also similar between groups. Immunohistochemistry revealed that iNOS expression was abundant throughout the heart in WT mice on day 1 after MI, particularly near the infarct borderzone. On day 7 after MI, E(cc) in KO mice was significantly improved in some borderzone sectors compared with WT. The LV volumes were significantly lower in KO mice at days 7 and 28 compared with WT. The EF on days 7 and 28 was significantly higher in KO mice compared with WT. The circumferential extent of wall thinning was also significantly reduced in KO versus WT mice at days 7 and 28., Conclusions: Expression of iNOS contributes importantly to post-infarction contractile dysfunction and subsequent LV remodeling, suggesting new strategies to combat heart failure resulting from large MI.

Cardiac magnetic resonance (CMR) imaging can provide noninvasive, high resolution images of heart anatomy, viability, perfusion, and function. However, the adoption of clinical CMR imaging protocols for small rodents has been limited due to the small heart size and rapid heart rates. Therefore, most CMR studies in small rodents have been performed on non-clinical, high-field MR magnets. Because such high-field systems are not readily available at most institutions, the technical aspects that are needed to perform CMR on clinical 1.5 T and 3.0 T MR scanners are presented in this paper. Equipment requirements are presented, and a comprehensive description of the methods needed to complete a CMR exam including the animal preparation, imaging, and image analysis are discussed. In addition, the advanced applications of myocardial tagging and delayed-contrast-enhanced imaging are reviewed for the assessment of regional contractile function and myocardial viability, respectively.

In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance-trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic beta-cells and to monitor, non-invasively in real-time, hepatic delivery and engraftment by magnetic resonance imaging (MRI). Magnetocapsules were detected as single capsules with an altered magnetic resonance appearance on capsule rupture. Magnetocapsules were functional in vivo because mouse beta-cells restored normal glycemia in streptozotocin-induced diabetic mice and human islets induced sustained C-peptide levels in swine. In this large-animal model, magnetocapsules could be precisely targeted for infusion by using magnetic resonance fluoroscopy, whereas MRI facilitated monitoring of liver engraftment over time. These findings are directly applicable to ongoing improvements in islet cell transplantation for human diabetes, particularly because our magnetocapsules comprise clinically applicable materials.

In displacement-encoded imaging with stimulated echoes (DENSE), tissue displacement is encoded in the phase of the stimulated echo. However, three echoes generally contribute to the acquired signal (the stimulated echo, the complex conjugate of the stimulated echo, and an echo due to T(1) relaxation). It is usually desirable to suppress all except the stimulated echo, since otherwise the additional echoes will cause displacement measurement errors. Ideally, suppression of the artifact-generating echoes would be independent of time, T(1), and displacement-encoding frequency, and would not require additional acquisitions. In this study through-plane gradients were used to selectively dephase artifact-generating echoes without causing significant signal loss of the stimulated echo. A cine DENSE sequence was modified to include dephasing gradients and perform complementary spatial modulation of magnetization (CSPAMM). For single-acquisition cine DENSE using dephasing alone, artifact suppression was similar to CSPAMM with two acquisitions. The use of dephasing with CSPAMM required two acquisitions, but demonstrated greater artifact suppression than CSPAMM alone or dephasing alone., ((c) 2006 Wiley-Liss, Inc.)

Alginate-poly-L-lysine-alginate (APA) microcapsules have been explored as vehicles for therapeutic drug and cell delivery. The permselectivity of these capsules provides a unique means of controlled drug release and immunoisolation of encapsulated cells. Immunoisolation is especially attractive as it abrogates the need for chronic immunosuppressive therapy and opens up the possibility for the delivery of numerous cell sources including xenogeneic grafts. APA microcapsules containing cellular therapeutics have proven effective in the short-term treatment of a wide range of diseases requiring enzyme or endocrine replacement therapy, including type I diabetes. If these microcapsules could be noninvasively monitored with X-ray imaging modalities (i.e., fluoroscopy, CT, and digital subtraction angiography), questions such as the ideal transplantation site, the best means of delivery, and the long-term survival of grafts could be better addressed. We have developed two novel alginate-based radiopaque microcapsule formulations containing either barium sulfate (Ba X-Caps) or bismuth sulfate (Bi X-Caps). As compared to conventional, nonradiopaque APA capsules, Ba X-Caps and Bi X-Caps containing human cadaveric islets resulted in a decrease in cellular viability of less than 5% up to 14 days after encapsulation. Both radiopaque capsules were found to be permeable to lectins < or =75 kDa, but were impermeable to lectins > or =120 kDa, thus ensuring the blockage of the penetration of antibodies while allowing free diffusion of insulin and nutrients. The glucose-responsive insulin secretion of the radiopaque encapsulated human islets was found to be unaltered compared to that of unlabeled controls, with human C-peptide levels ranging from 3.21 to 2.87 (Ba X-Caps) and 3.23 to 2.87 (Bi X-Caps) ng/islet at 7 and 14 days postencapsulation, respectively. Using fluoroscopy, both Ba X-Caps and Bi X-Caps could be readily visualized as single radiopaque entities in vitro. Furthermore, following transplantation in vivo in mice and rabbits, single capsules could be identified with no significant change in contrast for at least 2 weeks. This study represents the first attempt at making radiopaque microcapsules for X-ray guided delivery and imaging of cellular therapeutics. While human cadaveric islets were used as a proof-of-principle, these radiopaque capsules may have wide ranging therapeutic applications for a variety of cell types.

The relative contribution of the angiotensin II type 1 and 2 receptors (AT1-R and AT2-R) in postmyocardial infarction (MI) remodeling remains incompletely understood. We studied five groups of C57Bl/6 mice after 1 h of left anterior descending artery occlusion-reperfusion: 1) wild type, untreated (n = 12); 2) wild type, treated with the AT1-R blocker losartan (10-20 mg.kg(-1).day(-1) in drinking water) from day 1 to day 28 post-MI (n = 10); 3) cardiac overexpression of the AT2-R [AT2-transgenic (TG); n = 14]; 4) AT2-TG treated with losartan (n = 13); and 5) AT2-TG and null for the AT1a-R [AT2-TG/AT1 knockout (KO); n = 10]. Cardiac magnetic resonance imaging (CMR) measured ejection fraction and left ventricular end-diastolic and end-systolic volume (EDVI and ESVI) and mass indexed to weight on days 0, 1, 7, and 28 post-MI. Infarct size was measured on day 1 by late gadolinium-enhanced CMR. Regional myocyte hypertrophy and collagen content were measured on day 28 post-MI. Infarct size was similar among groups. Systolic blood pressure was lowest in AT2-TG/AT1KO. By day 28 post-MI, when corrected for baseline differences, EDVI and ESVI were higher and ejection fraction was lower in wild type than other groups. Ejection fraction was highest and EDVI and mass index were lowest in AT2-TG/AT1KO at day 28. The AT2-TG/AT1KO demonstrated less fibrosis in adjacent regions. Regional myocyte hypertrophy was similar in all groups. The AT1-R and AT2-R are intricately intertwined in post-MI remodeling. Pharmacological blockade of AT1-R is equivalent to AT2-R overexpression in attenuating post-MI remodeling. Genetic knockout of the AT1a-R is additive to AT2-R overexpression, due, at least in part, to blood pressure lowering.

A technique for fast imaging of regional myocardial function using a spiral acquisition in combination with strain-encoded (SENC) magnetic resonance imaging (MRI) is presented in this paper. This technique, which is termed fast-SENC, enables scan durations as short as a single heartbeat. A reduced field of view (FOV) without foldover artifacts was achieved by localized SENC, which selectively excited the region around the heart. The two images required for SENC imaging (low- and high-tuning) were acquired in an interleaved fashion throughout the cardiac cycle to further shorten the scan time. Regional circumferential contraction and longitudinal shortening of both the left ventricle (LV) and right ventricle (RV) were examined in long- and short-axis views, respectively. The in vivo results obtained from five human subjects and five infarcted dogs are presented. The results of the fast-SENC technique in a single heartbeat acquisition were comparable to those obtained by conventional SENC in a long acquisition time. Therefore, fast-SENC may prove useful for imaging during stress or arrhythmia., (Copyright 2006 Wiley-Liss, Inc.)

We developed mathematical modeling tools for mapping 3D infarct geometry from multislice late gadolinium enhancement data, allowing fusion with multislice MR tagging data, in mice with myocardial infarction. Five C57BL/6 mice were imaged at baseline, 1, 7 and 28 days after 60 min occlusion of the left anterior descending coronary artery. The 3D infarct geometry was mapped in material coordinates, and registered with 3D strain, showing permanent dysfunction in infarcted segments, intermediate function in the adjacent zone, and maintained function in the remote zone. 3D mapping of late enhancement and strain allows registration of multiple studies in a consistent framework.

Cardiac MRI is an accurate, noninvasive modality for assessing the structure and function of the murine heart. In addition to conventional imaging, MRI tissue tracking methods can quantify numerous aspects of myocardial mechanics, including intramyocardial displacement, strain, twist, and torsion. In the present study, we developed and applied a novel pulse sequence based on displacement-encoded imaging using stimulated echoes (DENSE) that achieves multislice coverage, high spatial resolution, and three-dimensional (3D) displacement encoding. With the use of this technique, myocardial mechanics of C57Bl/6 mice were measured at baseline and 1 day after experimental myocardial infarction. At baseline, the mean systolic transmural circumferential strain was -0.14 +/- 0.02 and the mean systolic radial strain was 0.30 +/- 0.05. Changes in circumferential and radial strains from the subepicardium to the subendocardium were detected at baseline (P < 0.05). One day after infarction, significantly reduced 3D displacements and strain were detected in infarcted and noninfarcted myocardium. Infarction also reduced normalized systolic torsion from its baseline value of 1.35 +/- 0.27 degrees /mm (R = 0.99) to 0.07 +/- 0.54 degrees /mm (R = 0.96, P < 0.05). DENSE MRI can assess the 3D myocardial mechanics of the murine heart in <1 h of scan time at 4.7 T and may be applied to studies of myocardial mechanics in genetically engineered mice.

Angiotensin II type 2 receptor (AT2-R) overexpression in the mouse heart preserves left ventricular (LV) size and global LV function during post-MI remodeling. We hypothesized that CMR tagging would localize regional improvements in myocardial function during post-MI remodeling in AT2-R cardiac overexpressed transgenic mice (TG), which could explain the preservation of global LV function post-MI. Six male wild-type (WT) C57BL/6 mice and 10 TG mice were studied by CMR at baseline (day 0) and days 1, 7, and 28 post-MI. MI was induced by 1 hour occlusion of the LAD followed by reperfusion. On day 1 post-MI, gadolinium-DTPA was injected to assess infarct size. LV size and function was assessed by cine CMR. Mean % circumferential shortening (%CS) was calculated within infarcted, adjacent, and remote regions at each time point in WT and TG mice. Quantitative interstitial collagen and mean myocyte cross-sectional area was measured postmortem at day 28 post-MI. LV end-systolic volume was lower and ejection fraction higher at baseline in the TG group and these differences were maintained post-MI. Within infarcted and remote zones, although %CS was higher in TG mice at day 0, there was no difference by day 28 between groups. Within adjacent regions, while there was no difference at day 0 or 1 in TG vs. WT, %CS was significantly higher in TG mice by day 7, and these changes persisted out to day 28 post-MI. Regional interstitial collagen and myocyte size were similar between groups. Thus, myocardial tagging can detect regional differences in contractile function post-MI in TG mice, and AT2-R overexpression is associated with improved contractile function in adjacent noninfarcted myocardium.

Displacement-encoded imaging with stimulated echoes (DENSE) and harmonic phase imaging (HARP) employ 1-1 spatial modulation of magnetization to cosine modulate the longitudinal magnetization as a function of position at end diastole. Later in the cardiac cycle they sample the cosine-modulated signal and compute myocardial strain from the signal phase. The sampled signal generally includes three distinct echoes: 1) a displacement-encoded stimulated echo, 2) the complex conjugate of the displacement-encoded echo, and 3) an echo arising from T1 relaxation. If the T1-relaxation and complex conjugate echoes are suppressed, then a phase image representing just the displacement-encoded echo can be reconstructed. In the present study, the use of cosine and sine modulation to eliminate (CANSEL) the T1-relaxation and complex conjugate echoes was investigated. With the use of CANSEL, it was demonstrated that DENSE accurately measures through-plane as well as in-plane components of tissue motion. Also, DENSE with CANSEL artifact suppression can provide increased signal-to-noise ratio (SNR) secondary to reduced intravoxel dephasing by using relatively low displacement-encoding frequencies. For applications that employ DENSE imaging with multiple acquisitions, the CANSEL technique can suppress artifact-generating echoes without placing constraints on the displacement-encoding frequency and direction.

A new technique was developed to increase the signal-to-noise ratio (SNR) in displacement encoding with stimulated echoes (DENSE) MRI. This signal-averaged DENSE (sav-DENSE) technique is based on the SNR advantage of extracting a pair of DENSE images with uncorrelated noise from the complex complementary spatial modulation of the magnetization image, and combining them during image reconstruction. Eleven healthy volunteers were imaged at three short-axis locations with the use of sav-DENSE, cine DENSE, and myocardial tagging pulse sequences. In this study, sav-DENSE increased the SNR by 15-34% as compared to cine DENSE. Circumferential strain values measured by sav-DENSE and myocardial tagging were strongly correlated (slope = 0.95, intercept = -0.02, R = 0.92) and within the 95% limits of agreement. The breath-hold sav-DENSE technique yielded relatively accurate and precise quantification of 2D intramyocardial function, with a 40.2-ms temporal resolution and a 3.5 x 3.5 mm2 spatial resolution., (Copyright 2004 Wiley-Liss, Inc.)

MRI is emerging as an important modality for assessing myocardial function in transgenic and knockout mouse models of cardiovascular disease, including myocardial infarction (MI). Displacement encoding with stimulated echoes (DENSE) measures myocardial motion at high spatial resolution using phase-reconstructed images. The current DENSE technique uses inversion recovery (IR) to suppress T(1)-relaxation artifacts; however, IR is ill-suited for contrast-enhanced infarct imaging in the heart, where multiple T(1) values are observed. We have developed a modified DENSE method employing complementary acquisitions for T(1)-independent artifact suppression. With this technique, displacement and strain are measured in phase-reconstructed images, and contrast-enhanced regions of infarction are depicted in perfectly coregistered magnitude-reconstructed images. The displacement measurements and T(1)-weighted image contrast were validated with the use of a rotating phantom. Modified DENSE was performed in mice (N = 9) before and after MI. Circumferential (E(cc)) and radial (E(rr)) strain were measured, and contrast-enhanced infarcted myocardium was detected by DENSE. At baseline, E(cc) was -0.16 +/- 0.01 and E(rr) was 0.39 +/- 0.07. After MI, E(cc) was 0.04 +/- 0.02 and E(rr) was 0.03 +/- 0.04 in infarcted regions, whereas E(cc) was -0.12 +/- 0.02 and E(rr) was 0.38 +/- 0.09 in noninfarcted regions. In vivo E(cc) as determined by DENSE correlated well with E(cc) obtained by conventional tag analysis (R = 0.90)., (Copyright 2004 Wiley-Liss, Inc.)

Background: The objective of this study was to noninvasively determine the effects of reperfused myocardial infarction (MI) on regional and global left-ventricular (LV) function 24 hours after MI in intact mice with contrast-enhanced cardiac MRI and a single, gradient-echo pulse sequence., Methods and Results: Twenty-three mice received baseline MRI scans followed by either 60 minutes of coronary occlusion (MI group, n=15) or thoracotomy without occlusion (sham group, n=8). Gadolinium-DTPA-enhanced magnetic resonance (MR) images were acquired 24 hours after surgery. Hearts were then excised for conventional infarct size determination via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. In addition to infarct size, analysis of the MR images yielded left ventricular (LV) mass, LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), cardiac output, and percent LV wall thickening (%WTh). Twenty-four hours after surgery, infarct size was 28.1+/-1.8% of LV mass by MRI and 27.5+/-1.7% by TTC (P=NS). Bland-Altman analysis revealed close agreement between the results obtained by the 2 methods. MI had little effect on LVEDV but caused a 98% increase in LVESV (from 11.3 to 22.4 microL, P<0.05), which resulted in a significant reduction in LVEF (from 70% to 37%, P<0.05). Compared with LV regional function at baseline, %WTh 24 hours after MI was significantly depressed, not only in infarcted myocardium but also in regions remote from the infarct zone. In contrast, sham-operated mice showed a small but significant increase in %WTh 24 hours after surgery (P<0.05)., Conclusions: MRI can accurately assess both infarct size and cardiac function in intact mice early after large, reperfused MI, revealing the existence of contractile dysfunction in noninfarcted regions of the heart.

A breath-hold two-dimensional cine magnetic resonance (MR) pulse sequence based on displacement encoding with stimulated echoes (DENSE) for quantitative myocardial motion tracking was developed and evaluated. In the sequence, complementary spatial modulation of magnetization was used for time-independent artifact suppression, and echo-planar imaging was used for rapid data sampling. Twelve healthy volunteers underwent cine DENSE MR imaging, and six of them also underwent conventional MR imaging myocardial tagging. The circumferential shortening component of strain (E(cc)) was measured on cine DENSE MR images and conventional tagged MR images. With complementary spatial modulation of magnetization, 10% or less of the total cine DENSE MR image energy was attributed to an artifact-generating echo during systolic imaging. Two-dimensional intramyocardial displacement and strain were measured at cine DENSE MR imaging with spatial resolution and temporal resolution of 2.7 x 2.7 mm and 60 msec, respectively. E(cc) measured at cine DENSE MR imaging correlated well with that measured at conventional MR imaging tagging (slope = 0.88, intercept = 0.00, R = 0.87)., (Copyright RSNA, 2004)

We hypothesized that nitric oxide (NO) mediates the benefits of cardiac angiotensin II type 2 (AT(2)-R) overexpression during postmyocardial infarction (post-MI) remodeling. Eleven wild-type (WT) C57BL/6 mice and 28 transgenic (TG) mice with AT(2)-R overexpression were studied by cardiac magnetic resonance imaging (CMR) at baseline and days 1 and 28 post-MI induced by left anterior descending artery occlusion and reperfusion. Sixteen TG mice were treated from day 1 through 28 post-MI with the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester in drinking water at 1 mg/mL (TG-Rx). Left ventricular mass index (LVMI), end-diastolic volume index (EDVI) and end-systolic volume index (ESVI), wall thickness, percent thickening, and ejection fraction (EF) were measured. Infarct size on day 1 was assessed by post-contrast CMR. Interstitial collagen was quantified in noninfarcted regions. At baseline, heart rate (HR), blood pressure (BP), LVMI, EDVI, and ESVI were similar between groups, as were infarct size and weekly post-MI HR and systolic BP. By day 28 post-MI, EDVI and ESVI were similar in WT and TG-Rx, but significantly lower in TG (ESVI: 1.41+/-0.18 microL/g versus 2.53+/-0.14 microL/g in WT; 2.17+/-0.14 microL/g in TG-Rx; P<0.008 for both). At day 28, EF was higher in TG (46.3%+/-2.9%) compared with WT and TG-Rx (32.7+/-2.3% and 33.7+/-2.3, respectively; P<0.003 for both). Wall thickening at day 28 post-MI was greater in the base and mid-LV in TG than WT and TG-Rx. Noninfarcted region interstitial collagen was similar between groups. Thus, the NO pathway may mediate much of the benefits of cardiac AT(2)-R overexpression during post-MI remodeling.

Increasing production by increasing milking frequency (MF) is a management option available to dairy producers. This study examined effects of MF and interactions with region and herd size on measures of herd performance. Dairy Herd Improvement (DHI) Holstein herd summary records (n = 10,754, 10,550, and 10,438) for the years 1998, 1999, and 2000 were classified by MF: two times a day (2X) milking vs three times a day (3X); herd size: small (< 250 cows) and large (> or = 250 cows); and region: North and South. Percentage of herds milking 3X by year were 7.0, 6.7, and 7.1. Rolling herd average milk production was 16, 16, and 15% higher for herds milking 3X than herds milking 2X for the respective years. Herds milking 3X in the North region outproduced herds milking 3X in the South region. Milk fat and protein percentages were lower for herds milking 3X during all 3 yr. Differences in energy-corrected milk production between herds milking 3X and herds milking 2X were 14.5, 13.4, and 13.4% during the respective 3 yr as a result of lower component percentages for herds milking 3X. Herds milking 3X had more days open and higher actual calving intervals than herds milking 2X. Services per pregnancy for herds breeding primarily by artificial insemination were higher for herds milking 3X than for herds milking 2X. Somatic cell scores and weighted somatic cell counts were lower for herds milking 3X than herds milking 2X. Herds milking 3X had a higher percentage of somatic cell scores in the low range (0 to 3) and a lower percentage in the high range (7 to 9). Mean percentages of cows entering and leaving the herd were higher for herds milking 3X during all 3 yr.

The purpose of this study was to use MR myocardial tagging to assess regional cardiac function after myocardial infarction (MI) in mice. Eight mice were imaged before and 1 day after MI. MRI included cine imaging, myocardial tagging, and contrast-enhanced imaging. Regional percent circumferential shortening (%CS) was measured from the tagged images, and the region of hyperenhancement on the contrast-enhanced images was used to determine the infarcted, adjacent, and remote zones. Ejection fraction (EF) fell from 59% +/- 6% at baseline to 32% +/- 6% after MI (P < 0.01). At baseline, %CS was 14.5% +/- 3.4%. After MI, %CS was 0.7% +/- 4.4% in the infarcted zone, 7.4% +/- 4.4% in the adjacent zone, and 11.8% +/- 4.2% in the remote zone. %CS was statistically different for all comparisons between the infarcted, adjacent, remote, and baseline groups (P < 0.01). MR tagging can detect regional differences in myocardial function post-MI in mice., (Copyright 2002 Wiley-Liss, Inc.)

This study evaluated the utility of cardiac MRI for assessing the impact of myocardial infarction (MI) on cardiac structure and function in mice following reperfused 1- or 2-hr occlusions of the left anterior descending coronary artery (LAD). When assessed 1 day after MI, the left ventricular ejection fraction (LVEF) had declined by more than half, and remained depressed for the duration of the study. Furthermore, MI initiated dramatic increases in both LV end-systolic volume (LVESV) and end-diastolic volume (LVEDV), with a greater than threefold increase in LVESV and a twofold increase in LVEDV by 4 weeks post-MI. Transmural LV wall thickening (WTh) analysis revealed that noninfarcted myocardium in the remote septal region exhibited an early deficit in contractile function after MI that transiently resolved by day 7, only to be followed by a late phase of dysfunction that became fully manifest by day 28 post-MI. In conclusion, MRI allows the serial assessment of cardiac structure and function after MI in mice, with a resolution adequate to document both regional and temporal changes. The application of these imaging techniques in transgenic and knock-out mice will greatly expedite research aimed at defining the functional roles of individual genes in the pathophysiology of LV remodeling (LVR) after reperfused MI., (Copyright 2002 Wiley-Liss, Inc.)

Forty clinically normal lactating Holstein cattle from a herd involved in a natural outbreak of chronic nitrate toxicosis were divided into 2 equal groups according to production, stage of lactation, age, and apparent pregnancy state (pregnant or nonpregnant). One group was fed a low-nitrate ration (average of 356 ppm on dry matter basis in concentrate; less than 400 ppm in free-choice hay for 1st 5 wks of study). The 2nd group was fed a high-nitrate (HN) ration (average of 1,600 ppm in protein concentrate-amemded corn silage; 4,000 ppm in free-choice hay for the 8-week study). At the end of the study, the 2 groups were classified according to their starting reproductive status: nonpregnant (open); early pregnant (less than 60 da); midpregnant (average of 105 da). Milk production, milk fat, and milk nitrate concentrations were similar for cows fed both rations. Serum progesterone concentration (SPC) was depressed (P less than 0.05) in cows fed the HN ration. This effect was prominent in open, luteal phase cows, less prominent but still apparent in early pregnant cows, and absent in midpregnant cows. The early reproductive problems of chronic nitrate toxicosis may be due to depression of SPC. A possible mechanism of inhibition of luteal progesterone synthesis by inhibition of cytochrome P-450 is presented.