A radial sampling strategy for uniform k‐space coverage with retrospective respiratory gating in 3D ultrashort‐echo‐time lung imaging

The purpose of this work was to develop a 3D radial‐sampling strategy which maintains uniform k‐space sample density after retrospective respiratory gating, and demonstrate its feasibility in free‐breathing ultrashort‐echo‐time lung MRI. A multi‐shot, interleaved 3D radial sampling function was designed by segmenting a single‐shot trajectory of projection views such that each interleaf samples k‐space in an incoherent fashion. An optimal segmentation factor for the interleaved acquisition was derived based on an approximate model of respiratory patterns such that radial interleaves are evenly accepted during the retrospective gating. The optimality of the proposed sampling scheme was tested by numerical simulations and phantom experiments using human respiratory waveforms. Retrospectively, respiratory‐gated, free‐breathing lung MRI with the proposed sampling strategy was performed in healthy subjects. The simulation yielded the most uniform k‐space sample density with the optimal segmentation factor, as evidenced by the smallest standard deviation of the number of neighboring samples as well as minimal side‐lobe energy in the point spread function. The optimality of the proposed scheme was also confirmed by minimal image artifacts in phantom images. Human lung images showed that the proposed sampling scheme significantly reduced streak and ring artifacts compared with the conventional retrospective respiratory gating while suppressing motion‐related blurring compared with full sampling without respiratory gating. In conclusion, the proposed 3D radial‐sampling scheme can effectively suppress the image artifacts due to non‐uniform k‐space sample density in retrospectively respiratory‐gated lung MRI by uniformly distributing gated radial views across the k‐space. Copyright © 2016 John Wiley & Sons, Ltd.     

Hepatic arterial spin labelling MRI: an initial evaluation in mice

The development of strategies to combat hepatic disease and augment tissue regeneration has created a need for methods to assess regional liver function. Liver perfusion imaging has the potential to fulfil this need, across a range of hepatic diseases, alongside the assessment of therapeutic response. In this study, the feasibility of hepatic arterial spin labelling (HASL) was assessed for the first time in mice at 9.4 T, its variability and repeatability were evaluated, and it was applied to a model of colorectal liver metastasis. Data were acquired using flow‐sensitive alternating inversion recovery‐arterial spin labelling (FAIR‐ASL) with a Look–Locker readout, and analysed using retrospective respiratory gating and a T₁‐based quantification. This study shows that preclinical HASL is feasible and exhibits good repeatability and reproducibility. Mean estimated liver perfusion was 2.2 ± 0.8 mL/g/min (mean ± standard error, n = 10), which agrees well with previous measurements using invasive approaches. Estimates of the variation gave a within‐session coefficient of variation (CV_WS) of 7%, a between‐session coefficient of variation (CV_BS) of 9% and a between‐animal coefficient of variation (CV_A) of 15%. The within‐session Bland–Altman repeatability coefficient (RC_WS) was 18% and the between‐session repeatability coefficient (RC_BS) was 29%. Finally, the HASL method was applied to a mouse model of liver metastasis, in which significantly lower mean perfusion (1.1 ± 0.5 mL/g/min, n = 6) was measured within the tumours, as seen by fluorescence histology. These data indicate that precise and accurate liver perfusion estimates can be achieved using ASL techniques, and provide a platform for future studies investigating hepatic perfusion in mouse models of disease. Copyright © 2014 John Wiley & Sons, Ltd.     

Time‐efficient measurement of multi‐phase arterial spin labeling MR signal in white matter

White matter (WM) perfusion has great potential as a physiological biomarker in many neurological diseases. Although it has been demonstrated previously that arterial spin labeling magnetic resonance imaging (ASL‐MRI) enables the detection of the perfusion‐weighted signal in most voxels in WM, studies of cerebral blood flow (CBF) in WM by ASL‐MRI are relatively scarce because of its particular challenges, such as significantly lower perfusion and longer arterial transit times relative to gray matter (GM). Recently, ASL with a spectroscopic readout has been proposed to enhance the sensitivity for the measurement of WM perfusion. However, this approach suffers from long acquisition times, especially when acquiring multi‐phase ASL datasets to improve CBF quantification. Furthermore, the potential increase in the signal‐to‐noise ratio (SNR) by spectroscopic readout compared with echo planar imaging (EPI) readout has not been proven experimentally. In this study, we propose the use of time‐encoded pseudo‐continuous ASL (te‐pCASL) with single‐voxel point‐resolved spectroscopy (PRESS) readout to quantify WM cerebral perfusion in a more time‐efficient manner. Results are compared with te‐pCASL with a conventional EPI readout for both WM and GM perfusion measurements. Perfusion measurements by te‐pCASL PRESS and conventional EPI showed no significant difference for quantitative WM CBF values (Student's t‐test, p = 0.19) or temporal SNR (p = 0.33 and p = 0.81 for GM and WM, respectively), whereas GM CBF values (p = 0.016) were higher using PRESS than EPI readout. WM CBF values were found to be 18.2 ± 7.6 mL/100 g/min (PRESS) and 12.5 ± 5.5 mL/100 g/min (EPI), whereas GM CBF values were found to be 77.1 ± 11.2 mL/100 g/min (PRESS) and 53.6 ± 9.6 mL/100 g/min (EPI). This study demonstrates the feasibility of te‐pCASL PRESS for the quantification of WM perfusion changes in a highly time‐efficient manner, but it does not result in improved temporal SNR, as does traditional te‐pCASL EPI, which remains the preferred option because of its flexibility in use.     

In vivo MRI for effective non‐invasive detection and follow‐up of an orthotopic mouse model of lung cancer

One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this study, we evaluated the potential of optimized lung MRI techniques as a completely non‐invasive approach for non‐small‐cell lung cancer (NSCLC) MRI in vivo detection and follow‐up in a mouse model of lung adenocarcinoma expressing the luciferase gene. Bioluminescent lung tumour cells were orthotopically implanted in immuno‐deficient mice. Ultra‐short echo‐time (UTE) MRI free‐breathing acquisitions were compared with standard gradient‐echo lung MRI (FLASH) using both respiratory‐gated and free‐breathing protocols. The MRI findings were validated against bioluminescence imaging (BLI) and gold‐standard histopathology analysis. Adenocarcinoma‐like pathological tissue was successfully identified in all the mice with gated‐FLASH and non‐gated UTE MRI, and good tumour co‐localization was found between MRI, BLI and histological analyses. An excellent or good correlation was found between the measured bioluminescent signal and the total tumour volumes quantified with UTE MRI or gated‐FLASH MRI, respectively. No significant correlation was found when the tumours were segmented on non‐gated MR FLASH images. MRI was shown to be a powerful imaging tool able to detect, quantify and longitudinally monitor the development of sub‐millimetric NSCLCs. To our knowledge, this is the first study which proves the feasibility of a completely non‐invasive MRI quantitative detection of lung adenocarcinoma in freely breathing mice. The absence of ionizing radiation and the high‐resolution of MRI, along with the complete non‐invasiveness and good reproducibility of the proposed non‐gated protocol, make this imaging tool ideal for direct translational applications. Copyright © 2014 John Wiley & Sons, Ltd.     

High‐sensitivity cerebral perfusion mapping in mice by kbGRASE‐FAIR at 9.4 T

The combination of flow‐sensitive alternating inversion recovery (FAIR) and single‐shot k‐space‐banded gradient‐ and spin‐echo (kbGRASE) is proposed here to measure perfusion in the mouse brain with high sensitivity and stability. Signal‐to‐noise ratio (SNR) analysis showed that kbGRASE‐FAIR boosts image and temporal SNRs by 2.01 ± 0.08 and 2.50 ± 0.07 times, respectively, when compared with standard single‐shot echo planar imaging (EPI)‐FAIR implemented in our experimental systems, although the practically achievable spatial resolution was slightly reduced. The effects of varying physiological parameters on the precision and reproducibility of cerebral blood flow (CBF) measurements were studied following changes in anesthesia regime, capnia and body temperature. The functional MRI time courses with kbGRASE‐FAIR showed a more stable response to 5% CO₂ than did those with EPI‐FAIR. The results establish kbGRASE‐FAIR as a practical and robust protocol for quantitative CBF measurements in mice at 9.4 T. Copyright © 2010 John Wiley & Sons, Ltd.     

Arterial spin labeling‐fast imaging with steady‐state free precession (ASL‐FISP): a rapid and quantitative perfusion technique for high‐field MRI

Arterial spin labeling (ASL) is a valuable non‐contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo‐planar imaging (EPI) or true fast imaging with steady‐state free precession (true FISP) readouts, which are prone to off‐resonance artifacts on high‐field MRI scanners. We have developed a rapid ASL‐FISP MRI acquisition for high‐field preclinical MRI scanners providing perfusion‐weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow‐sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL‐FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high‐field MRI scanners with minimal image artifacts. Copyright © 2014 John Wiley & Sons, Ltd.     

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo‐echo planar imaging (SE‐EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE‐EPI MRE sequence. A paired t‐test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland–Altman's analysis were performed to determine the reproducibility and repeatability of the SE‐EPI MRE‐derived shear stiffness measurements. The SE‐EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE‐EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.     

Three‐dimensional accurate detection of lung emphysema in rats using ultra‐short and zero echo time MRI

Emphysema is a life‐threatening pathology that causes irreversible destruction of alveolar walls. In vivo imaging techniques play a fundamental role in the early non‐invasive pre‐clinical and clinical detection and longitudinal follow‐up of this pathology. In the present study, we aimed to evaluate the feasibility of using high resolution radial three‐dimensional (3D) zero echo time (ZTE) and 3D ultra‐short echo time (UTE) MRI to accurately detect lung pathomorphological changes in a rodent model of emphysema.Porcine pancreas elastase (PPE) was intratracheally administered to the rats to produce the emphysematous changes. 3D ZTE MRI, low and high definition 3D UTE MRI and micro‐computed tomography images were acquired 4 weeks after the PPE challenge. Signal‐to‐noise ratios (SNRs) were measured in PPE‐treated and control rats. T₂* values were computed from low definition 3D UTE MRI. Histomorphometric measurements were made after euthanizing the animals. Both ZTE and UTE MR images showed a significant decrease in the SNR measured in PPE‐treated lungs compared with controls, due to the pathomorphological changes taking place in the challenged lungs. A significant decrease in T₂* values in PPE‐challenged animals compared with controls was measured using UTE MRI. Histomorphometric measurements showed a significant increase in the mean linear intercept in PPE‐treated lungs. UTE yielded significantly higher SNR compared with ZTE (14% and 30% higher in PPE‐treated and non‐PPE‐treated lungs, respectively).This study showed that optimized 3D radial UTE and ZTE MRI can provide lung images of excellent quality, with high isotropic spatial resolution (400 µm) and SNR in parenchymal tissue (>25) and negligible motion artifacts in freely breathing animals. These techniques were shown to be useful non‐invasive instruments to accurately and reliably detect the pathomorphological alterations taking place in emphysematous lungs, without incurring the risks of cumulative radiation exposure typical of micro‐computed tomography. Copyright © 2015 John Wiley & Sons, Ltd.     

Glycoprotein nonmetastatic B as a prognostic indicator in small cell lung cancer

Glycoprotein nonmetastatic melanoma B (GPNMB) is a type I transmembrane glycoprotein which is overexpressed in many tumors and seems to play a critical role in metastasis of malignant tumors. The purpose of this study was to determine GPNMB expression in small cell lung cancer (SCLC) and analyze the prognostic value in patients with SCLC. A total of 132 cases of SCLCs were analyzed immunohistochemically on tissue microarrays (TMAs). Patients were divided into weak‐positive and strong‐positive GPNMB groups. In addition, serum GPNMB was evaluated by enzyme‐linked immunosorbent assay (ELISA). The average serum GPNMB concentration was 1054.15 ± 363.71 pg/mL in the weak‐positive group, 2611.52 ± 457.57 pg/mL in the strong‐positive group, and 427.61 ± 273.9 pg/mL in the control. The strong‐positive group showed significantly higher serum GPNMB levels than the weak‐positive group and healthy control (p < 0.01). Overall survival in the weak‐positive GPNMB group was significantly longer than in the strong‐positive group (27 months vs 15 months, p < 0.01). These results suggest that the expression of GPNMB may be useful as a prognostic indicator in patients with SCLC.     

Fast volumetric imaging of bound and pore water in cortical bone using three‐dimensional ultrashort‐TE (UTE) and inversion recovery UTE sequences

We report the three‐dimensional ultrashort‐TE (3D UTE) and adiabatic inversion recovery UTE (IR‐UTE) sequences employing a radial trajectory with conical view ordering for bi‐component T₂* analysis of bound water (T₂*^BW) and pore water (T₂*^PW) in cortical bone. An interleaved dual‐echo 3D UTE acquisition scheme was developed for fast bi‐component analysis of bound and pore water in cortical bone. A 3D IR‐UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two‐dimensional UTE (2D UTE) and IR‐UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3‐T scanner. Bi‐component fitting of 3D UTE images of bovine samples showed a mean T₂*^BW of 0.26 ± 0.04 ms and T₂*^PW of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR‐UTE signal showed a single‐component decay with a mean T₂*^BW of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR‐UTE sequences. Bi‐component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T₂*^BW of 0.32 ± 0.08 ms and T₂*^PW of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single‐component fitting of 3D IR‐UTE images showed a mean T₂*^BW of 0.35 ± 0.09 ms. The 3D UTE and 3D IR‐UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.     

SElf‐gated Non‐Contrast‐Enhanced FUnctional Lung imaging (SENCEFUL) using a quasi‐random fast low‐angle shot (FLASH) sequence and proton MRI

Obtaining functional information on the human lung is of tremendous interest in the characterization of lung defects and pathologies. However, pulmonary ventilation and perfusion maps usually require contrast agents and the application of electrocardiogram (ECG) triggering and breath holds to generate datasets free of motion artifacts. This work demonstrates the possibility of obtaining highly resolved perfusion‐weighted and ventilation‐weighted images of the human lung using proton MRI and the SElf‐gated Non‐Contrast‐Enhanced FUnctional Lung imaging (SENCEFUL) technique. The SENCEFUL technique utilizes a two‐dimensional fast low‐angle shot (FLASH) sequence with quasi‐random sampling of phase‐encoding (PE) steps for data acquisition. After every readout, a short additional acquisition of the non‐phase‐encoded direct current (DC) signal necessary for self‐gating was added. By sorting the quasi‐randomly acquired data according to respiratory and cardiac phase derived from the DC signal, datasets of representative respiratory and cardiac cycles could be accurately reconstructed. By application of the Fourier transform along the temporal dimension, functional maps (perfusion and ventilation) were obtained. These maps were compared with dynamic contrast‐enhanced (DCE, perfusion) as well as standard Fourier decomposition (FD, ventilation) reference datasets. All datasets were additionally scored by two experienced radiologists to quantify image quality. In addition, one initial patient examination using SENCEFUL was performed. Functional images of healthy volunteers and a patient diagnosed with hypoplasia of the left pulmonary artery and left‐sided pulmonary fibrosis were successfully obtained. Perfusion‐weighted images corresponded well to DCE‐MRI data; ventilation‐weighted images offered a significantly better depiction of the lung periphery compared with standard FD. Furthermore, the SENCEFUL technique hints at a potential clinical relevance by successfully detecting a perfusion defect in the patient scan. It can be concluded that SENCEFUL enables highly resolved ventilation‐ and perfusion‐weighted maps of the human lung to be obtained using proton MRI, and might be interesting for further clinical evaluation. Copyright © 2014 John Wiley & Sons, Ltd.     

Three‐dimensional ultrashort echo time cones T1ρ (3D UTE‐cones‐T1ρ) imaging

We report a novel three‐dimensional (3D) ultrashort echo time (UTE) sequence employing Cones trajectory and T_1ρ preparation (UTE‐Cones‐T_1ρ) for quantitative T_1ρ assessment of short T₂ tissues in the musculoskeletal system. A basic 3D UTE‐Cones sequence was combined with a spin‐locking preparation pulse for T_1ρ contrast. A relatively short TR was used to decrease the scan time, which required T₁ measurement and compensation using 3D UTE‐Cones data acquisitions with variable TRs. Another strategy to reduce the total scan time was to acquire multiple Cones spokes (N_sp) after each T_1ρ preparation and fat saturation. Four spin‐locking times (TSL = 0–20 ms) were acquired over 12 min, plus another 7 min for T₁ measurement. The 3D UTE‐Cones‐T_1ρ sequence was compared with a two‐dimensional (2D) spiral‐T_1ρ sequence for the imaging of a spherical CuSO₄ phantom and ex vivo meniscus and tendon specimens, as well as the knee and ankle joints of healthy volunteers, using a clinical 3‐T scanner. The CuSO₄ phantom showed a T_1ρ value of 76.5 ± 1.6 ms with the 2D spiral‐T_1ρ sequence, as well as 85.7 ± 3.6 and 89.2 ± 1.4 ms for the 3D UTE‐Cones‐T_1ρ sequences with N_sp of 1 and 5, respectively. The 3D UTE‐Cones‐T_1ρ sequence provided shorter T_1ρ values for the bovine meniscus sample relative to the 2D spiral‐T_1ρ sequence (10–12 ms versus 16 ms, respectively). The cadaveric human Achilles tendon sample could only be imaged with the 3D UTE‐Cones‐T_1ρ sequence (T_1ρ = 4.0 ± 0.9 ms), with the 2D spiral‐T_1ρ sequence demonstrating near‐zero signal intensity. Human studies yielded T_1ρ values of 36.1 ± 2.9, 18.3 ± 3.9 and 3.1 ± 0.4 ms for articular cartilage, meniscus and the Achilles tendon, respectively. The 3D UTE‐Cones‐T_1ρ sequence allows volumetric T_1ρ measurement of short T₂ tissues in vivo.     

Left ventricular blood flow patterns at rest and under dobutamine stress in healthy pigs

Intracardiac blood flow patterns are affected by the morphology of cardiac structures and are set up to support the heart's pump function. Exercise affects contractility and chamber size as well as pre‐ and afterload. The aim of this study was to test the feasibility of four‐dimensional phase contrast cardiovascular MRI under pharmacological stress and to study left ventricular blood flow under stress. 4D flow data were successfully acquired and analysed in 12 animals. During dobutamine infusion, heart rate and ejection fraction increased (82 ± 5 bpm versus 124 ± 3 bpm/46 ± 9% versus 65 ± 7%; both p < 0.05). A decrease in left ventricular end‐diastolic volume (72 ± 14 mL versus 55 ± 8 mL; p < 0.05) and end‐systolic volume (40 ± 15 mL versus 19 ± 6 mL; p < 0.05) but no change in stroke volume were observed. Trans‐mitral diastolic inflow velocity increased under dobutamine and the trajectory of inflowing blood was directed towards the anterior septum with increased inflow angle (26 ± 5°) when compared with controls (15 ± 2°). In 5/6 animals undergoing stress diastolic vortices developed later, and in 3/6 animals vortices collapsed earlier with significantly smaller cross‐sectional area during diastole. The vorticity index was not affected. Under the stress condition direct flow (% ejection within the next heart beat) increased from 43 ± 6% to 53 ± 8%. 4D MRI blood flow acquisition and analysis are feasible in pig hearts under dobutamine‐induced stress. Flow patterns characterized by high blood velocity and antero‐septally oriented diastolic inflow as well as decreased ventricular volumes are unfavourable conditions for diastolic vortex development under pharmacological stress, and cardiac output is increased by a rise in heart rate and directly ejected left ventricular blood volume.     

Impact of respiratory pattern on lung mechanics and interstitial proteoglycans in spontaneously breathing anaesthetized healthy rats

Aim: The aim of this study was to investigate the effect of different pattern of spontaneous breathing on the respiratory mechanics and on the integrity of the pulmonary extracellular matrix. Methods: Experiments were performed on adult healthy rats in which different spontaneously breathing pattern was elicited through administration of two commonly used anaesthetic mixtures: pentobarbital/urethane (P/U) and ketamine/medetomidine (K/M). The animals (five per group) were randomized and left to spontaneously breath for 10 min (P/U‐sham; K/M‐sham) or for 4 h (P/U‐4 h; K/M‐4 h), targeting the anaesthesia level to obtain a tidal volume of about 8 mL kg^?1 body wt. At the end of the experiment, lung matrix integrity was assessed through determination of the glycosaminoglycans (GAGs) content in the lung parenchyma. Results: Compared with K/M, anaesthesia with P/U cocktail induced: (1) a higher respiratory rate and minute ventilation attained with lower P_aCO₂; (2) a higher pressure‐time‐product and work of breathing per minute; (3) a lower static lung compliance; (4) an increased activation of lung tissue metalloproteases; and (5) greater extraction of pulmonary interstitial GAGs. Conclusions: This study suggests that the breathing pattern induced by the different anaesthetic regimen may damage the pulmonary interstitium even during spontaneous breathing at physiological tidal volumes.     

Ultrashort‐TE MRI longitudinal study and characterization of a chronic model of asthma in mice: inflammation and bronchial remodeling assessment

Asthma is a chronic disease characterized by bronchial hyperresponsiveness (BHR), bronchial inflammation and remodeling. The great improvements in ¹H MRI ultrashort‐TE (UTE) sequences in the last decade have allowed lung images with high‐resolution and good signal‐to‐noise ratio to be obtained in parenchymal tissues. In this article, we present a UTE ¹H MRI high‐resolution study of a chronic model of asthma in mice with the aim to longitudinally assess the main features of asthma using a fully noninvasive approach. Balb/c mice (n = 6) were sensitized with ovalbumin over a period of 75 days. The control group (n = 3) received normal saline on the same days. MRI acquisitions were performed on days 0, 38 and 78 to study the inflammatory volumes and bronchial remodeling (peribronchial signal intensity index, PBSI). Plethysmographic studies were performed on days 0, 39 and 79 to assess BHR to methacholine using the enhanced pause (Penh) ratio. The average inflammatory volume measured by MRI in the ovalbumin group (15.6 ± 2.4 μL) was increased significantly relative to control mice (–0.3 ± 0.7 μL) on day 38. The inflammatory volume was larger (34.2 ± 3.1 μL) on day 78 in the ovalbumin group. PBSI was significantly higher in the ovalbumin group on day 78 (1.53 ± 0.08) relative to the control group (1.16 ± 0.10), but not on day 38. After sensitization, asthmatic mice presented BHR to methacholine on days 39 and 79. Penh ratios correlated significantly with the inflammatory volume on day 39 and with the PBSI on day 79. This study shows, for the first time, that high‐resolution UTE ¹H MRI of the lungs may allow the noninvasive quantification of peribronchial eosinophilic inflammation with airways occlusion by mucus and of bronchial remodeling in a murine asthma model that correlates with functional parameters. Copyright © 2013 John Wiley & Sons, Ltd.     

Quantitative mouse renal perfusion using arterial spin labeling

Information on renal perfusion is essential for the diagnosis and prognosis of kidney function. Quantification using gadolinium chelates is limited as a result of filtration through renal glomeruli and safety concerns in patients with kidney dysfunction. Arterial spin labeling MRI is a noninvasive technique for perfusion quantification that has been applied to humans and animals. However, because of the low sensitivity and vulnerability to motion and susceptibility artifacts, its application to mice has been challenging. In this article, mouse renal perfusion was studied using flow‐sensitive alternating inversion recovery at 7 T. Good perfusion image quality was obtained with spin‐echo echo‐planar imaging after controlling for respiratory, susceptibility and fat artifacts by triggering, high‐order shimming and water excitation, respectively. High perfusion was obtained in the renal cortex relative to the medulla, and signal was absent in scans carried out post mortem. Cortical perfusion increased from 397 ± 36 (mean ± standard deviation) to 476 ± 73 mL/100 g/min after switching from 100% oxygen to carbogen with 95% oxygen and 5% carbon dioxide. The perfusion in the medulla was 2.5 times lower than that in the cortex and changed from 166 ± 41 mL/100 g/min under oxygen to 203 ± 40 mL/100 g/min under carbogen. T₁ decreased in both the cortex (from 1570 ± 164 to 1377 ± 72 ms, p < 0.05) and medulla (from 1788 ± 107 to 1573 ± 144 ms, p < 0.05) under carbogen relative to 100% oxygen. The results showed the potential of the use of ASL for perfusion quantification in mice and in models of renal diseases. Copyright © 2013 John Wiley & Sons, Ltd.     

Volumetric imaging of myelin in vivo using 3D inversion recovery‐prepared ultrashort echo time cones magnetic resonance imaging

Direct myelin imaging is promising for characterization of multiple sclerosis (MS) brains at diagnosis and in response to therapy. In this study, a 3D inversion recovery‐prepared ultrashort echo time cones (IR‐UTE‐Cones) sequence was used for both morphological and quantitative imaging of myelin on a clinical 3 T scanner. Myelin powder phantoms with different myelin concentrations were imaged with the 3D UTE‐Cones sequence and it showed a strong correlation between concentrations and UTE‐Cones signals, demonstrating the ability of the UTE‐Cones sequence to directly image myelin in the brain. Quantitative myelin imaging with multi‐echo IR‐UTE‐Cones sequences show similar T₂* values for a D₂O‐exchanged myelin phantom (T₂* = 0.33 ± 0.04 ms), ex vivo brain specimens (T₂* = 0.20 ± 0.04 ms) and in vivo healthy volunteers (T₂* = 0.254 ± 0.023 ms), further confirming the feasibility of 3D IR‐UTE‐Cones sequences for direct myelin imaging in vivo. In ex vivo MS brain study, signal loss is observed in MS lesions, which was confirmed with histology. For the in vivo study, the lesions in MS patients also show myelin signal loss using the proposed direct myelin imaging method, demonstrating the clinical potential for MS diagnosis. Furthermore, the measured IR‐UTE‐Cones signal intensities show a significant difference between normal‐appearing white matter in MS patients and normal white matter in volunteers, which cannot be found in clinical used T₂‐FLAIR sequences. Thus, the proposed 3D IR‐UTE‐Cones sequence showed clinical potential for MS diagnosis with the capability of direct myelin detection of the whole brain.     

Optimization of flow‐sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain

Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow‐sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain. Copyright © 2012 John Wiley & Sons, Ltd.     

Feasibility of quantitative ultrashort echo time (UTE)‐based methods for MRI of peripheral nerve

Peripheral nerves are a composite tissue consisting of neurovascular elements packaged within a well‐organized extracellular matrix. Their composition, size, and anatomy render nerves a challenging medical imaging target. In contrast to morphological MRI, which represents the predominant approach to nerve imaging, quantitative MRI sequences can provide information regarding tissue composition. Here, we applied standard clinical Carr‐Purcell‐Meiboom‐Gill (CPMG) and experimental three‐dimensional (3D) ultrashort echo time (UTE) Cones sequences for quantitative nerve imaging including T₂ measurement with single‐component analysis, T₂* measurement with single‐component and bi‐component analyses, and magnetization transfer ratio (MTR) analysis. We demonstrated the feasibility and the high quality of single‐component T₂*, bi‐component T₂*, and MTR approaches to analyze nerves imaged with clinically deployed 3D UTE Cones pulse sequences. For 24 single fascicles from eight nerves, we measured a mean single‐component T₂* of 22.6 ±8.9 ms, and a short T₂* component (STC) with a mean T₂* of 1.7 ±1.0 ms and a mean fraction of (6.74 ±4.31)% in bi‐component analysis. For eight whole nerves, we measured a mean single‐component T₂* of 16.7 ±2.2 ms, and an STC with a mean T₂* of 3.0 ±1.0 ms and a mean fraction of (15.56 ±7.07)% in bi‐component analysis. For nine fascicles from three healthy nerves, we measured a mean MTR of (25.2 ±1.9)% for single fascicles and a mean MTR of (23.6 ±0.9)% for whole nerves. No statistically significant correlation was observed between any MRI parameter and routine histological outcomes, perhaps due to the small sample size and lack of apparent sample pathology. Overall, we have successfully demonstrated the feasibility of measuring quantitative MR outcomes ex vivo, which might reflect features of nerve structure and macromolecular content. These methods should be validated comprehensively on a larger and more diverse set of nerve samples, towards the interpretation of in vivo outcomes. These approaches have new and broad implications for the management of nerve disease, injury, and repair.     

Feasibility of coronary endothelial function assessment using arterial spin labeled CMR

Coronary endothelial dysfunction (CED) is an independent predictor of cardiovascular disease, but its assessment has been limited to invasive coronary angiography. Myocardial perfusion imaging using arterial spin labeled (ASL) cardiac magnetic resonance (CMR) may be an effective non‐invasive alternative for detection of CED. Thirty‐four patients were recruited: 10 healthy volunteers, 13 at high‐risk for coronary artery disease (CAD), and 11 with established CAD. ASL‐CMR was performed continuously in a single mid‐short axis slice during rest, stress, and recovery. Stress was induced with sustained isometric handgrip exercise, an endothelial dependent stressor. Myocardial perfusion (MP) during rest, peak stress, and recovery were calculated and compared. After excluding subjects unable to complete the protocol or who exhibited poor data quality, 6 healthy, 10 high‐risk, and 7 CAD patients were included in the analysis. Average MP (ml/g/min) was 1.31 ± 1.23, 1.61 ± 1.12, and 1.40 ± 0.97 at rest, and 1.64 ± 1.49, 2.31 ± 1.61, and 2.84 ± 1.77 during stress, for the CAD, high‐risk and healthy group, respectively. The average MP response (MP_stress – MP_rest, ml/g/min) was 0.32 ± 1.93, 0.69 ± 1.34, and 1.44 ± 1.46 for CAD, high‐risk and healthy group, respectively. MP during handgrip stress was significantly lower for both the CAD (p = 0.0005) and high‐risk groups (p = 0.05) compared to the healthy volunteers. In only the healthy subjects, MP was significantly higher in stress compared to rest (p = 0.0002). Participants with CAD had significantly lower MP response compared to healthy volunteers, as detected by ASL‐CMR. These findings support the feasibility of ASL‐CMR for non‐invasive assessment of CED.