Can texture analysis in ultrashort echo-time MRI distinguish primary graft dysfunction from acute rejection in lung transplants? A multidimensional assessment in a mouse model.

BACKGROUND: Differentiation of early postoperative complications affects treatment options after lung transplantation. PURPOSE: To assess if texture analysis in ultrashort echo-time (UTE) MRI allows distinction of primary graft dysfunction (PGD) from acute transplant rejection (ATR) in a mouse lung transplant model. STUDY TYPE: Longitudinal. ANIMAL MODEL: Single left lung transplantation was performed in two cohorts of six mice (strain C57BL/6) receiving six syngeneic (strain C57BL/6) and six allogeneic lung transplants (strain BALB/c (H-2Kd )). FIELD STRENGTH/SEQUENCE: 4.7T small-animal MRI/eight different UTE sequences (echo times: 50-5000 µs) at three different postoperative timepoints (1, 3, and 7 days after transplantation). ASSESSMENT: Nineteen different first- and higher-order texture features were computed on multiple axial slices for each combination of UTE and timepoint (24 setups) in each mouse. Texture features were compared for transplanted (graft) and contralateral native lungs between and within syngeneic and allogeneic cohorts. Histopathology served as a reference. STATISTICAL TESTS: Nonparametric tests and correlation matrix analysis were used. RESULTS: Pathology revealed PGD in the syngeneic and ATR in the allogeneic cohort. Skewness and low-gray-level run-length features were significantly different between PGD and ATR for all investigated setups (P < 0.03). These features were significantly different between graft and native lung in ATR for most setups (minimum of 20/24 setups; all P < 0.05). The number of significantly different features between PGD and ATR increased with elapsing postoperative time. Differences in significant features were highest for an echo-time of 1500 µs. DATA CONCLUSION: Our findings suggest that texture analysis in UTE-MRI might be a tool for the differentiation of PGD and ATR in the early postoperative phase after lung transplantation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:108-116.

[Imaging of the peripheral nervous system]. / Bildgebung des peripheren Nervensystems.

Imaging of the peripheral nervous system Abstract. With the technical advances in imaging achieved in recent years, the significance of radiology in everyday clinical practice has become definitely increased. This also applies to the diagnosis and evaluation of neuropathies. Highly sensitive electrophysiology is increasingly complemented by specific imaging. Therapy-relevant information from imaging includes the localization and cause, but also the distribution pattern of a neuropathy. Neurography helps to increase diagnostic certainty and is an important part in management of patients with neuropathy. In this article we would like to present the possibilities and the value of different imaging modalities including ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI).

Diffusion tensor imaging of the abdominal organs: Influence of oriented intravoxel flow compartments.

Water flow in partially oriented intravoxel compartments mimics an anisotropic fast-diffusion regime, which contributes to the signal attenuation in diffusion-weighted images. In the abdominal organs, this flow may reflect physiological fluid movements (eg, tubular urine flow in kidneys, or bile flow through the liver) and have a clinical relevance. This study investigated the influence of anisotropic intravoxel water flow on diffusion tensor imaging (DTI) of the abdominal organs. Diffusion-weighted images were acquired in five healthy volunteers using an EPI sequence with diffusion preparation (TR/TE: 1000 ms/71 ms; b-values: 0, 10, 20, 40, 70, 120, 250, 450, 700, 1000 s/mm2 ; 12 noncollinear diffusion-encoding directions). DTI of liver and kidneys was performed assuming (i) monoexponential decay of the diffusion-weighted signal, and (ii) accounting for potential anisotropy of the fast-diffusion compartments using a tensorial generalization of the IVIM model. Additionally, potential dependency of the metrics of the tensors from the anatomical location was evaluated. Significant differences in the metrics of the diffusion tensor (DT) were found in both liver and kidneys when comparing the two models. In both organs, the trace and the fractional anisotropy of the DT were significantly higher in the monoexponential model than when accounting for perfusion. The comparison of areas of the liver proximal to the hilum with distal regions and of renal cortex with the medulla also proved a location dependency of the size of the fast-diffusion compartments. Pseudo-diffusion correction in DTI enables the assessment of the solid parenchyma regardless of the organ perfusion or other pseudo-diffusive fluid movements. This may have a clinical relevance in the assessment of parenchymal pathologies (eg, liver fibrosis). The fast pseudo-diffusion components present a detectable anisotropy, which may reflect the hepatic microcirculation or other sources of mesoscopic fluid movement in the abdominal organs.

Investigation of the pulsatility of cerebrospinal fluid using cardiac-gated Intravoxel Incoherent Motion imaging.

The quantitative and non-invasive monitoring of cerebrospinal fluid (CSF) dynamics and composition may have high clinical relevance in the management of CSF disorders. In this study, we propose the use of the Intravoxel Incoherent Motion (IVIM) MRI for obtaining simultaneous measurements of CSF self-diffusion and fluid circulation. The rationale for this study was that turbulent fluid and mesoscopic fluid fluctuations can be modeled in a first approximation as a fast diffusion process. In this case, we expect that the fast fluid circulation and slower molecular diffusion dynamics can be quantified, assuming a bi-exponential attenuation pattern of the diffusion-weighted signal in MRI. IVIM indexes of fast and slow diffusion measured at different sites of the CSF system were systematically evaluated depending on both the phase of the heart cycle and the direction of the diffusion-encoding. The IVIM measurements were compared to dynamic measurements of fluid circulation performed by phase-contrast MRI. Concerning the dependence on the diffusion/flow-encoding direction, similar patterns were found both in the fraction of fast diffusion, f, and in the fluid velocity. Generally, we observed a moderate to high correlation between the fraction of fast diffusion and the maximum fluid velocity along the high-flow directions. Exploratory data analysis detected similarities in the dependency of the fraction of fast diffusion and of the velocity from the phase of the cardiac cycle. However, no significant differences were found between parameters measured during different phases of the cardiac cycle. Our results suggest that the fraction of fast diffusion may reflect CSF circulation. The bi-exponential IVIM model potentially allows us to disentangle the two diffusion components of the CSF dynamics by providing measurements of fluid cellularity (via the slow-diffusion coefficient) and circulation (via the fraction of fast-diffusion index).

Is there evidence for more than two diffusion components in abdominal organs? - A magnetic resonance imaging study in healthy volunteers.

The most commonly applied model for the description of diffusion-weighted imaging (DWI) data in perfused organs is bicompartmental intravoxel incoherent motion (IVIM) analysis. In this study, we assessed the ground truth of underlying diffusion components in healthy abdominal organs using an extensive DWI protocol and subsequent computation of apparent diffusion coefficient 'spectra', similar to the computation of previously described T2 relaxation spectra. Diffusion datasets of eight healthy subjects were acquired in a 3-T magnetic resonance scanner using 68 different b values during free breathing (equidistantly placed in the range 0-1005 s/mm2 ). Signal intensity curves as a function of the b value were analyzed in liver, spleen and kidneys using non-negative least-squares fitting to a distribution of decaying exponential functions with minimum amplitude energy regularization. In all assessed organs, the typical slow- and fast-diffusing components of the IVIM model were detected [liver: true diffusion D = (1.26 ± 0.01) × 10-3 mm2 /s, pseudodiffusion D* = (270 ± 44) × 10-3 mm2 /s; kidney cortex: D = (2.26 ± 0.07) × 10-3 mm2 /s, D* = (264 ± 78) × 10-3 mm2 /s; kidney medulla: D = (1.57 ± 0.28) × 10-3 mm2 /s, D* = (168 ± 18) × 10-3 mm2 /s; spleen: D = (0.91 ± 0.01) × 10-3 mm2 /s, D* = (69.8 ± 0.50) × 10-3 mm2 /s]. However, in the liver and kidney, a third component between D and D* was found [liver: D' = (43.8 ± 5.9) × 10-3 mm2 /s; kidney cortex: D' = (23.8 ± 11.5) × 10-3 mm2 /s; kidney medulla: D' = (5.23 ± 0.93) × 10-3 mm2 /s], whereas no third component was detected in the spleen. Fitting with a diffusion kurtosis model did not lead to a better fit of the resulting curves to the acquired data compared with apparent diffusion coefficient spectrum analysis. For a most accurate description of diffusion properties in the liver and the kidneys, a more sophisticated model seems to be required including three diffusion components.

Cardiac-gated intravoxel incoherent motion diffusion-weighted magnetic resonance imaging for the investigation of intracranial cerebrospinal fluid dynamics in the lateral ventricle: a feasibility study.

PURPOSE: Intravoxel incoherent motion (IVIM) in diffusion-weighted magnetic resonance imaging (DW-MRI) attributes the signal attenuation to the molecular diffusion and to a faster pseudo-diffusion. Purpose of the study was to demonstrate the feasibility of IVIM for the investigation of intracranial cerebrospinal fluid (CSF) dynamics. METHODS: Cardiac-gated DW-MRI images with fifteen b-values (0-1300s/mm2) along three orthogonal directions (mediolateral (ML), anteroposterior (AP), and craniocaudal (CC)) were acquired during maximum systole and diastole in 10 healthy volunteers (6 males, mean age 36 ± 15 years). A pixel-wise bi-exponential fitting with an iterative nonparametric algorithm was carried out to calculate the following parameters: diffusion coefficient (D), fast diffusion coefficient (D*), and fraction of fast diffusion (f). Region of interest measurements were performed in both lateral ventricles. Comparison of IVIM parameters was performed among two cardiac cycle acquisitions and among the diffusion-encoding directions using a paired Student's t test. RESULTS: f significantly (p < 0.05) depended on the diffusion-encoding direction and on the cardiac cycle (diastole AP 0.30 ± 0.13, ML 0.22 ± 0.12, CC 0.26 ± 0.17; systole AP 0.45 ± 0.17, ML 0.34 ± 0.15, CC 0.40 ± 0.21). Neither a cardiac cycle nor a direction dependency was found among mean D values (which is in line with the expected intraventricular isotropic diffusion) and D* values (p > 0.05 each). CONCLUSION: The fraction of fast diffusion from IVIM is feasible to detect a direction-dependent and cardiac-dependent pulsatile CSF flow within the lateral ventricles allowing for quantitative monitoring of CSF dynamics. This technique might provide opportunities to further investigate the pathophysiology of various neurological disorders involving altered CSF dynamics.

Separation of collagen-bound and porous bone-water longitudinal relaxation in mice using a segmented inversion recovery zero-echo-time sequence.

PURPOSE: Cortical bone mechanical properties are related to the collagen-bound water (CBW) and pore water (PW) components of cortical bone. The study evaluates the feasibility of zero-echo-time imaging in mice in vivo for longitudinal relaxation time (T1) measurements in cortical bone and separation of CBW and PW components. METHODS: Zero-echo-time data were acquired at 4.7 Tesla in six mice with 14 different inversion times (0-2,600 ms). Region-of-interest analysis was performed at level of femur diaphysis. The T1 of cortical bone and of CBW (T1cbw) and PW (T1pw) as well as the CBW fraction (cbwf) was computed using a mono-exponential and a bi-exponential fitting approach, respectively. The sum of the squared residuals (Res) to the fit was provided for both approaches. RESULTS: For the mono-exponential model, mean T1 ± standard deviation (SD) was 1,057 ± 160 ms. The bi-exponential approach provided a reliable separation of two different bone-water components, with a mean T1cbw of 213 ± 95 ms, T1pw of 2,152 ± 894 ms, and cbwf of 7.4 ± 2.7 %. Lower Res was obtained with bi-exponential approach (P < 0.001), and Res mean values ± SD were 0.016 ± 0.007 (bi-exponential) and 0.033 ± 0.016 (mono-exponential). CONCLUSION: Zero-echo-time imaging allows for longitudinal relaxation measurements of cortical bone in vivo in mice models, with a reliable separation of PW and CBW components using a bi-exponential curve fitting approach. Magn Reson Med 77:1909-1915, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Diffusion-weighted imaging of the abdomen: Impact of b-values on texture analysis features.

The purpose of this work was to systematically assess the impact of the b-value on texture analysis in MR diffusion-weighted imaging (DWI) of the abdomen. In eight healthy male volunteers, echo-planar DWI sequences at 16 b-values ranging between 0 and 1000 s/mm2 were acquired at 3 T. Three different apparent diffusion coefficient (ADC) maps were computed (0, 750/100, 390, 750 s/mm2 /all b-values). Texture analysis of rectangular regions of interest in the liver, kidney, spleen, pancreas, paraspinal muscle and subcutaneous fat was performed on DW images and the ADC maps, applying 19 features computed from the histogram, grey-level co-occurrence matrix (GLCM) and grey-level run-length matrix (GLRLM). Correlations between b-values and texture features were tested with a linear and an exponential model; the best fit was determined by the smallest sum of squared residuals. Differences between the ADC maps were assessed with an analysis of variance. A Bonferroni-corrected p-value less than 0.008 (=0.05/6) was considered statistically significant. Most GLCM and GLRLM-derived texture features (12-18 per organ) showed significant correlations with the b-value. Four texture features correlated significantly with changing b-values in all organs (p < 0.008). Correlation coefficients varied between 0.7 and 1.0. The best fit varied across different structures, with fat exhibiting mostly exponential (17 features), muscle mostly linear (12 features) and the parenchymatous organs mixed feature alterations. Two GLCM features showed significant variability in the different ADC maps. Several texture features vary systematically in healthy tissues at different b-values, which needs to be taken into account if DWI data with different b-values are analyzed. Histogram and GLRLM-derived texture features are stable on ADC maps computed from different b-values.

Intravoxel incoherent motion imaging measurement of perfusion changes in the parotid gland provoked by gustatory stimulation: A pilot study.

PURPOSE: To demonstrate the feasibility of intravoxel incoherent motion imaging (IVIM) for quantification of perfusion changes in the parotid gland after gustatory stimulation. MATERIALS AND METHODS: Eight healthy volunteers underwent diffusion-weighted magnetic resonance imaging (MRI) of the neck at 3T with 11 dynamic acquisitions (9 b-values between 0 and 980 s/mm2 , 2:40 min each). After 5:20 minutes, a lemon-mint-drop was administered orally. Perfusion fraction (Fp ), pseudodiffusion (D*), tissue diffusion (Dt ) coefficients, and optimal b-value threshold were measured using a multistep variable b-value threshold fitting approach. Dynamic changes in the coefficients between three exemplary timepoints (baseline, after stimulation, after dissolution) were compared using a Mann-Whitney U-test with Bonferroni correction (P < 0.016 significance level). RESULTS: Mean values (95% confidence interval [CI]) for IVIM parameters at baseline were Fp : 0.11 (0.08-0.15), D*: 56.48 mm2 /s (39.71-98.27), Dt : 1.01 mm2 /s (0.84-1.06), b-value threshold: 30 s/mm2 (21.25-105). After stimulation: Fp 0.16 (0.15-0.24; P < 0.01), D* 93.83 mm2 /s (77.98-129.53, P = 0.25), Dt 0.93 mm2 /s (0.87-1.08, P = 0.94), b-value threshold 20 s/mm2 (13.75-26.25 s/mm2 , P = 0.10), reflecting the increase in tissue perfusion. After dissolution of the drop: Fp : 0.13 (0.11-0.18, P = 0.38), D*: 101.61 mm2 /s (90.68-144.55, P = 0.07), Dt : 0.91 mm2 /s (0.85-1.05, P = 0.64), b-value threshold: 15 s/mm2 (11.25-40, P = 0.38). CONCLUSION: The IVIM method allows for simultaneous quantification of changes in perfusion and diffusion effects after gustatory stimulation of the parotid gland. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:570-578.

Magnetization Transfer MR Imaging to Monitor Muscle Tissue Formation during Myogenic in Vivo Differentiation of Muscle Precursor Cells.

Purpose To determine whether magnetization transfer (MT) magnetic resonance (MR) imaging may serve as a quantitative measure of the degree of fiber formation during differentiation of muscle precursor cells into engineered muscle tissue as a potential noninvasive monitoring tool in mice. Materials and Methods The study was approved by the local ethics committee (no. StV 01/2008) and the local Veterinary Office (license no. 99/2013). Human muscle progenitor cells (hMPCs) derived from rectus abdominis muscles were subcutaneously injected into CD-1 nude mice (CD-1 nude mice, Crl:CD1-Foxn1nu; Charles River Laboratories, Wilmington, Mass) for development of muscle tissue. The mice underwent MR imaging examinations at 4.7 T at days 1, 3, 7, 14, 21, and 28 after cell transplantation by using a gradient-echo sequence with an MT prepulse and systematic variation of the off-resonance frequency (50-37 500 Hz) at an amplitude of 800°. Direct saturation was estimated from a Bloch equation simulation. The MT ratio (MTR) was correlated to immunohistochemistry findings, Western blot results, and results of myography. Data were analyzed by using one-way or two-way analysis of variance with the Sidak or Tukey multiple comparisons test. Results In the reference skeletal muscle, highest MT was found for 2500 Hz off-resonance frequency with an MTR ± standard deviation of 57.5% ± 3.5. The developing muscle tissue exhibited increasing MT values during the 28 days of myogenic in vivo differentiation and did not reach the values of native skeletal muscle. Mean values of MTR (2500 Hz) for hMPCs were 27.6% ± 6.3 (day 1), 24.7% ± 8.7 (day 3), 28.2% ± 5.7 (day 7), 35.9% ± 5.0 (day 14), 37.0% ± 7.9 (day 21), and 39.9% ± 8.1 (day 28). The results from MT MR imaging correlated qualitatively well with muscle tissue expression of specific skeletal markers, as well as muscle contractility. Conclusion MT MR imaging may be used to noninvasively monitor the process of myogenic in vivo differentiation of hMPCs as a biomarker of the quantity and quality of muscle fiber formation. © RSNA, 2016 Online supplemental material is available for this article.

In vivo magnetization transfer imaging of the lung using a zero echo time sequence at 4.7 Tesla in mice: Initial experience.

PURPOSE: The aim of the present study was to assess the feasibility of magnetization transfer-prepared zero echo time (ZTE) imaging of the lung in vivo at high field strength [4.7 Tesla) T] in mice. METHODS: Eighteen C57BL/10 mice underwent MRI examinations in a 4.7T MR-scanner. A three-dimensional ZTE sequence was applied for lung imaging combined with a Gaussian MT-prepulse, which was followed by a train of 100 ZTE imaging readouts. Degree of MT was assessed by calculation of the magnetization transfer ratio (MTR). Direct saturation was estimated using Bloch equation simulations based on T1 measurements. The line-width of pulmonary tissue was estimated using T2* measurements. RESULTS: Experimental MTR-values of nonpulmonary tissues obtained with ZTE exhibited the characteristics known from conventional MT-sequences (skeletal muscle and liver: high values; fatty tissue: low values). Lung tissue demonstrated MTR-values in between fatty tissue and liver tissue. Direct saturation could be estimated by the Bloch simulation; however, an adequate approximation was only possible for T2 values nearly in the range of parenchymal organs. CONCLUSION: Pulmonary MT measurements at high field strength using the proposed MT-ZTE sequence is feasible; however, estimation of direct saturation remains challenging. Magn Reson Med 76:156-162, 2016. © 2015 Wiley Periodicals, Inc.

Diffusional kurtosis MRI of the lower leg: changes caused by passive muscle elongation and shortening.

Diffusional kurtosis MRI (DKI) quantifies the deviation of water diffusion from a Gaussian distribution. We investigated the influence of passive elongation and shortening of the lower leg muscles on the DKI parameters D (diffusion coefficient) and K (kurtosis). After approval by the local ethics committee, eight healthy volunteers (age, 29.1 ± 2.9 years) underwent MRI of the lower leg at 3 T. Diffusion-weighted images were acquired with 10 different b values at three ankle positions (passive dorsiflexion 10°, neutral position 0°, passive plantar flexion 40°). Parametrical maps of D and K were obtained by voxel-wise fitting of the signal intensities using a non-linear Levenberg-Marquardt algorithm. D and K were measured in the tibialis anterior, medial and lateral gastrocnemius, and soleus muscles. In the neutral position, D and K values were in the range between 1.66-1.79 × 10(-3) mm(2) /s and 0.21-0.39, respectively. D and K increased with passive shortening, and decreased with passive elongation, which could also be illustrated on the parametrical maps. In dorsiflexion, D (p < 0.01) and K (p = 0.036) were higher in the tibialis anterior than in the medial gastrocnemius. In plantar flexion, the opposite was found for K (p = 0.035). DKI parameters in the lower leg muscles are significantly influenced by the ankle joint position, indicating that the diffusion of water molecules in skeletal muscle deviates from a Gaussian distribution depending on muscle tonus. Copyright © 2016 John Wiley & Sons, Ltd.

Separation of collagen-bound and porous bone water transverse relaxation in mice: proposal of a multi-step approach.

The separation and quantification of collagen-bound water (CBW) and pore water (PW) components of the cortical bone signal are important because of their different contribution to bone mechanical properties. Ultrashort TE (UTE) imaging can be used to exploit the transverse relaxation from CBW and PW, allowing their quantification. We tested, for the first time, the feasibility of UTE measurements in mice for the separation and quantification of the transverse relaxation of CBW and PW in vivo using three different approaches for T2 * determination. UTE sequences were acquired at 4.7 T in six mice with 10 different TEs (50-5000 µs). The transverse relaxation time T2 * of CBW (T2 *cbw ) and PW (T2 *pw ) and the CBW fraction (bwf) were computed using a mono-exponential (i), a standard bi-exponential (ii) and a new multi-step bi-exponential (iii) approach. Regions of interest were drawn at multiple levels of the femur and vertebral body cortical bone for each mouse. The sum of the normalized squared residuals (Res) and the homogeneity of variance were tested to compare the different methods. In the femur, approach (i) yielded mean T2 * ± standard deviation (SD) of 657 ± 234 µs. With approach (ii), T2 *cbw , T2 *pw and bwf were 464 ± 153 µs, 15 777 ± 10 864 µs and 57.6 ± 9.9%, respectively. For approach (iii), T2 *cbw , T2 *pw and bwf were 387 ± 108 µs, 7534 ± 2765 µs and 42.5 ± 6.2%, respectively. Similar values were obtained from vertebral bodies. Res with approach (ii) was lower than with the two other approaches (p < 0.007), but T2 *pw and bwf variance was lower with approach (iii) than with approach (ii) (p < 0.048). We demonstrated that the separation and quantification of cortical bone water components with UTE sequences is feasible in vivo in mouse models. The direct bi-exponential approach exhibited the best approximation to the measured signal curve with the lowest residuals; however, the newly proposed multi-step algorithm resulted in substantially lower variability of the computed parameters. Copyright © 2016 John Wiley & Sons, Ltd.

Magnetization transfer as a potential tool for the early detection of acute graft rejection after lung transplantation in mice.

PURPOSE: To investigate the value of magnetization transfer (MT) measurements for assessment of acute rejection (AR) in a murine lung transplantation model. MATERIALS AND METHODS: Thirty mice including 15 C57BL/10 mice serving as donors and 15 C57BL/6 mice as recipients were examined in this study. MT imaging datasets were acquired on a 4.7 Tesla small animal MR scanner using a three-dimensional zero echo time sequence with a Gaussian-shaped MT prepulse with 1000° or 3000° flip angle and systematic variation of off-resonance frequencies between 1000 and 15,000 Hz. After image acquisition, the images were qualitatively assessed, magnetization transfer ratio (MTR) values were calculated and lungs were taken for histologic examination including staining with hematoxylin/eosin, Masson's trichrome (collagen), and α-smooth muscle (fibroproliferative tissue) staining. RESULTS: Lung transplantation was successfully performed in all 15 mice. All animals showed AR characterized by the presence of interstitial mononuclear cell infiltrates. There were significant differences of MTR in lungs with and without AR (P = 0.007). With a flip angle of 1000°, the largest differences between the MTR of healthy lungs and lungs with AR were observed for an off-resonance frequency of 10,000 Hz (difference MTR 1.80%) and 15,000 Hz (1.91%) and with a flip angle of 3000° at off-resonance frequencies of 6000 Hz (1.37%) and 8000 Hz (1.70%). CONCLUSION: MT measurements may provide a tool for the quantitative assessment of AR. J. Magn. Reson. Imaging 2016;44:1091-1098.

Ultra-short echo-time magnetic resonance imaging distinguishes ischemia/reperfusion injury from acute rejection in a mouse lung transplantation model.

To investigate whether lung tissue characterization by ultra-short echo-time (UTE) magnetic resonance imaging (MRI) allows ischemia/reperfusion injury to be distinguished from acute rejection in a mouse lung transplantation model. After orthotopic lung transplantation with 6 mice receiving syngeneic (C57Bl/6) lung transplants and 6 mice receiving allogeneic (BALB/c) transplants, they underwent postoperative imaging using three-dimensional UTE-MRI (echo times TE = 50-5000 µs) and conventional T2-weighted fast spin-echo imaging. Quantitative T2* values of lung transplant parenchyma and spin density (SD) were compared by region-of-interest analysis. All samples underwent histological and immunohistochemical workup. In the allogeneic group, alveolar infiltration resulting from acute organ rejection was visualized in the UTE sequences. This was reflected by the quantitative measurements of SD and T2* values with higher values in the allogeneic group compared with the syngeneic group and nontransplanted lung at the first time point (24 h postoperative: Tx allogeneic group SD: 2133.9 ± 516; Tx syngeneic group SD: 1648.61 ± 271; P = 0.004; Tx allogeneic group T2*: 1710.16 ± 644 µs, Tx syngeneic group T2*: 577.16 ± 263 µs; P = <0.001). Changes caused by acute rejection after lung transplantation can be visualized and characterized using a UTE sequence due to different relaxation properties compared with both syngeneic lung transplants and normal lung tissue.

Whole-Body Diffusion Tensor Imaging: A Feasibility Study.

OBJECTIVE: The aim of this study was to demonstrate the feasibility of whole-body diffusion tensor imaging (DTI) as a promising tool for research applications, for instance, for investigation of systemic muscle diseases. MATERIALS AND METHODS: Twelve healthy volunteers (mean age, 26.6 years; range, 20-39 years) underwent whole-body magnetic resonance imaging at 3 T using an echo planar imaging sequence (b value, 400 s/mm) with 6 different spatial encoding directions. Coronal maps of DTI parameters including mean diffusivity, fractional anisotropy, and diffusion tensor eigenvalues (λ1-3) were generated using in-house MATLAB routines. Diffusion tensor imaging parameters were evaluated by region-of-interest analysis in skeletal muscle, cerebral gray and white matter, the kidneys, and the liver. RESULTS: The acquisition time was 79 minutes 12 seconds. The different organs could be clearly depicted on the parametrical maps. Exemplary values in skeletal muscle were mean diffusivity, 1.67 ± 0.16 × 10(-3) mm2/s; fractional anisotropy, 0.26 ± 0.03; λ1, 2.17 ± 0.20 × 10(-3) mm2/s; λ2, 1.64 ± 0.17 × 10(-3) mm2/s; and λ3, 1.22 ± 0.12 × 10(-3) mm2/s. CONCLUSION: Whole-body DTI is technically feasible. Further refinements are required to achieve a higher signal-to-noise ratio and improved spatial resolution. A possible clinical application could be the assessment of systemic myopathies.

Magnetization transfer imaging of cortical bone in vivo using a zero echo time sequence in mice at 4.7 T: a feasibility study.

OBJECTIVE: To investigate the feasibility of magnetization transfer (MT) imaging in mice in vivo for the assessment of cortical bone. MATERIALS AND METHODS: MT-zero echo time data were acquired at 4.7 T in six mice using MT preparation pulses with two different flip angles (FAs) and a series of ten different off-resonance frequencies (500-15000 Hz). Regions of interest were drawn at multiple levels of the femoral cortical bone. The MT ratio (MTR) was computed for each combination of FAs and off-resonance frequencies. T1 measurements were used to estimate the direct saturation (DS) using a Bloch equation simulation. Estimation of the absorption line width of cortical bone from T2* measurements was also performed. RESULTS: MTR values were higher using 3000° FA than 1000° FA. MTR values decreased toward higher off-resonance frequencies. Maximum mean MTR ± standard deviation (SD) of 58.57 ± 5.22 (range 50.44-70.61) was measured with a preparation pulse of 3000° and off-resonance frequency of 500 Hz. Maximum "true" MT effect was estimated at around 2-3 and 5 kHz, respectively, for 1000° and 3000° FA. Mean full width at half maximum ± SD of 577 ± 91 Hz was calculated for the absorption spectral line of the cortical bone. CONCLUSION: MT imaging can be used for the assessment of cortical bone in mice in vivo. DS effects are negligible using preparation pulses with off-resonance frequencies greater than 3 kHz.

Intravoxel incoherent motion analysis of abdominal organs: computation of reference parameters in a large cohort of C57Bl/6 mice and correlation to microvessel density.

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DW-MRI) combined with intravoxel incoherent motion (IVIM) analysis may be applied for assessment of organ lesions, diffuse parenchymal pathologies, and therapy monitoring. The aim of this study was to determine IVIM reference parameters of abdominal organs for translational research in a large cohort of C57Bl/6 laboratory mice. MATERIALS AND METHODS: Anesthetized mice (n = 29) were measured in a 4.7 T small-animal MR scanner with a diffusion-weighted echo-planar imaging sequence at the [Formula: see text]-values 0, 13, 24, 55, 107, 260, 514, 767, 1020 s/mm(2). IVIM analysis was conducted on the liver, spleen, renal medulla and cortex, pancreas, and small bowel with computation of the true tissue diffusion coefficient [Formula: see text], the perfusion fraction [Formula: see text], and the pseudodiffusion coefficient [Formula: see text]. Microvessel density (MVD) was assessed by immunohistochemistry (IHC) against panendothelial cell antigen CD31. RESULTS: Mean values of the different organs [[Formula: see text] (10(-3) mm(2)/s); [Formula: see text] (%); [Formula: see text] (10(-3) mm(2)/s); MVD (MV/mm(2))]: liver 1.15 ± 0.14; 14.77 ± 6.15; 50.28 ± 33.21, 2008.48 ± 419.43, spleen 0.55 ± 0.12; 9.89 ± 5.69; 24.46 ± 17.31; n.d., renal medulla 1.50 ± 0.20; 14.63 ± 4.07; 35.50 ± 18.01; 1231.88 ± 290.61, renal cortex 1.34 ± 0.18; 10.83 ± 3.70; 16.74 ± 6.74; 810.09 ± 193.50, pancreas 1.23 ± 0.22; 20.12 ± 7.46; 29.35 ± 17.82, 591.15 ± 86.25 and small bowel 1.06 ± 0.13; 16.48 ± 3.63; 15.31 ± 7.00; 420.50 ± 168.42. Unlike [Formula: see text] and [Formula: see text], [Formula: see text] correlates significantly with MVD (r = 0.90, p = 0.037). CONCLUSION: This systematic evaluation of murine abdominal organs with IVIM and MVD analysis allowed to establish reference parameters for future DW-MRI translational research studies on small-animal disease models.

Systematic analysis of the intravoxel incoherent motion threshold separating perfusion and diffusion effects: Proposal of a standardized algorithm.

PURPOSE: To systematically evaluate the dependence of intravoxel-incoherent-motion (IVIM) parameters on the b-value threshold separating the perfusion and diffusion compartment, and to implement and test an algorithm for the standardized computation of this threshold. METHODS: Diffusion weighted images of the upper abdomen were acquired at 3 Tesla in eleven healthy male volunteers with 10 different b-values and in two healthy male volunteers with 16 different b-values. Region-of-interest IVIM analysis was applied to the abdominal organs and skeletal muscle with a systematic increase of the b-value threshold for computing pseudodiffusion D*, perfusion fraction Fp, diffusion coefficient D, and the sum of squared residuals to the bi-exponential IVIM-fit. RESULTS: IVIM parameters strongly depended on the choice of the b-value threshold. The proposed algorithm successfully provided optimal b-value thresholds with the smallest residuals for all evaluated organs [s/mm2]: e.g., right liver lobe 20, spleen 20, right renal cortex 150, skeletal muscle 150. Mean D* [10(-3) mm(2)/s], Fp [%], and D [10(-3) mm(2)/s] values (±standard deviation) were: right liver lobe, 88.7 ± 42.5, 22.6 ± 7.4, 0.73 ± 0.12; right renal cortex: 11.5 ± 1.8, 18.3 ± 2.9, 1.68 ± 0.05; spleen: 41.9 ± 57.9, 8.2 ± 3.4, 0.69 ± 0.07; skeletal muscle: 21.7 ± 19.0; 7.4 ± 3.0; 1.36 ± 0.04. CONCLUSION: IVIM parameters strongly depend upon the choice of the b-value threshold used for computation. The proposed algorithm may be used as a robust approach for IVIM analysis without organ-specific adaptation.

Dynamic intravoxel incoherent motion imaging of skeletal muscle at rest and after exercise.

The purpose of this work was to demonstrate the feasibility of intravoxel incoherent motion imaging (IVIM) for non-invasive quantification of perfusion and diffusion effects in skeletal muscle at rest and following exercise. After IRB approval, eight healthy volunteers underwent diffusion-weighted MRI of the forearm at 3 T and eight different b values between 0 and 500 s/mm(2) with a temporal resolution of 57 s per dataset. Dynamic images were acquired before and after a standardized handgrip exercise. Diffusion (D) and pseudodiffusion (D*) coefficients as well as the perfusion fraction (FP ) were measured in regions of interest in the flexor digitorum superficialis and profundus (FDS/FDP), brachioradialis, and extensor carpi radialis longus and brevis muscles by using a multi-step bi-exponential analysis in MATLAB. Parametrical maps were calculated voxel-wise. Differences in D, D*, and FP between muscle groups and between time points were calculated using a repeated measures analysis of variance with post hoc Bonferroni tests. Mean values and standard deviations at rest were the following: D*, 28.5 ± 11.4 × 10(-3) mm(2) /s; FP , 0.03 ± 0.01; D, 1.45 ± 0.09 × 10(-3) mm(2) /s. Changes of IVIM parameters were clearly visible on the parametrical maps. In the FDS/FDP, D* increased by 289 ± 236% (p < 0.029), FP by 138 ± 58% (p < 0.01), and D by 17 ± 9% (p < 0.01). A significant increase of IVIM parameters could also be detected in the brachioradialis muscle, which however was significantly lower than in the FDS/FDP. After 20 min, all parameters were still significantly elevated in the FDS/FDP but not in the brachioradialis muscle compared with the resting state. The IVIM approach allows simultaneous quantification of muscle perfusion and diffusion effects at rest and following exercise. It may thus provide a useful alternative to other non-invasive methods such as arterial spin labeling. Possible fields of interest for this technique include perfusion-related muscle diseases, such as peripheral arterial occlusive disease.