Trajectory correction enables free-running chemical shift encoded imaging for accurate cardiac proton-density fat fraction quantification at 3T.

BACKGROUND: Metabolic diseases can negatively alter epicardial fat accumulation and composition, which can be probed using quantitative cardiac chemical shift encoded(CSE) MRI by mapping proton-density fat fraction (PDFF). To obtain motion-resolved high-resolution PDFF maps, we proposed a free-running cardiac CSE-MRI framework at 3T. To employ faster bipolar readout gradients, a correction for gradients imperfections was added using the gradient impulse response function (GIRF) and evaluated on intermediate images and PDFF quantification. METHODS: Ten minutes free-running cardiac 3D radial CSE-MRI acquisitions were compared in vitro and in vivo at 3T. Monopolar and bipolar readout gradients schemes provided 8 echoes (TE1/ΔTE = 1.16/1.96ms) and 13 echoes (TE1/ΔTE = 1.12/1.07ms), respectively. Bipolar-gradients free-running cardiac fat and water images and PDFF maps were reconstructed with or without GIRF-correction. PDFF values were evaluated in silico, in vitro on a fat/water phantom, and in vivo in 10 healthy volunteers and three diabetic patients. RESULTS: In monopolar mode, fat-water swaps were demonstrated in silico and confirmed in vitro. Using bipolar readout gradients, PDFF quantification was reliable and accurate with GIRF correction with a mean bias of 0.03% in silico and 0.36% in vitro while it suffered from artifacts without correction, leading to a PDFF bias of 4.9% in vitro and swaps in vivo. Using bipolar readout gradients, in vivo PDFF of epicardial adipose tissue was significantly lower than in subcutaneous fat (80.4±7.1% vs 92.5±4.3%, P<0.0001). CONCLUSION: Aiming for an accurate PDFF quantification, high-resolution free-running cardiac CSE-MRI imaging proved to benefit from bipolar echoes with k-space trajectory correction at 3T. This free-breathing acquisition framework enables to investigate epicardial adipose tissue PDFF in metabolic diseases.

Evaluation of a nnU-Net type automated clinical volumetric tumor segmentation tool for diffuse low-grade glioma follow-up.

BACKGROUND AND PURPOSE: Diffuse low-grade gliomas (DLGG) are characterized by a slow and continuous growth and always evolve towards an aggressive grade. Accurate prediction of the malignant transformation is essential as it requires immediate therapeutic intervention. One of its most precise predictors is the velocity of diameter expansion (VDE). Currently, the VDE is estimated either by linear measurements or by manual delineation of the DLGG on T2 FLAIR acquisitions. However, because of the DLGG's infiltrative nature and its blurred contours, manual measures are challenging and variable, even for experts. Therefore we propose an automated segmentation algorithm using a 2D nnU-Net, to 1) gain time and 2) standardize VDE assessment. MATERIALS AND METHODS: The 2D nnU-Net was trained on 318 acquisitions (T2 FLAIR & 3DT1 longitudinal follow-up of 30 patients, including pre- & post-surgery acquisitions, different scanners, vendors, imaging parameters…). Automated vs. manual segmentation performance was evaluated on 167 acquisitions, and its clinical interest was validated by quantifying the amount of manual correction required after automated segmentation of 98 novel acquisitions. RESULTS: Automated segmentation showed a good performance with a mean Dice Similarity Coefficient (DSC) of 0.82±0.13 with manual segmentation and a substantial concordance between VDE calculations. Major manual corrections (i.e., DSC<0.7) were necessary only in 3/98 cases and 81% of the cases had a DSC>0.9. CONCLUSION: The proposed automated segmentation algorithm can successfully segment DLGG on highly variable MRI data. Although manual corrections are sometimes necessary, it provides a reliable, standardized and time-winning support for VDE extraction to asses DLGG growth.

Mitigating slice cross-talk in multi-slice multi-echo spin echo T2 mapping.

PURPOSE: To investigate whether a T2 inter-slice variation could occur when a multi-slice multi-echo spin echo (MESE) sequence is used for image acquisition and to propose an enhanced method for reconstructing T2 maps that can effectively address and correct these variations. METHODS: Bloch simulations were performed accounting for the direct saturation effect to evaluate magnetization changes in multi-slice 2D MESE sequence. Experimental phantom scans were performed to validate these simulations. An improved version of the dictionary-based reconstruction approach was proposed, enabling the creation of a multi-slice dictionary of echo modulation curves (EMC). The corresponding method has been assayed considering inter-slice T2 variation with phantoms and in lower leg. RESULTS: Experimental and numerical study illustrate that direct saturation leads to a bias of EMCs. This bias during the T2 maps reconstructions using original single-slice EMC-dictionary method led to inter-slice T2 variation of 2.03% in average coefficient of variation (CV) in agarose phantoms, and up to 2.8% in vivo (for TR = 2 s, slice gap = 0%). A reduction of CV was observed when increasing the gap up to 100% (0.36% in phantoms, and up to 1.5% in vivo) or increasing TR up to 4 s (0.76% in phantoms, and up to 1.9% in vivo). Matching the multi-slice experimental data with multi-slice dictionaries provided a reduced CV of 0.54% in phantoms and up to 2.3% in vivo. CONCLUSION: T2 values quantified from multi-slice MESE images using single-slice dictionaries are biased. A dedicated multi-slice EMC method providing the appropriate dictionaries can reduce the inter-slice T2 variation.

Quantitative magnetization transfer MRI unbiased by on-resonance saturation and dipolar order contributions.

PURPOSE: To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases. METHODS: The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T1D ) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction [MPF], T2,f , T2,b , R, and free pool T1 ). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T1 . RESULTS: Bland-Altman analyses demonstrated a systematic underestimation of MPF (-2.5% and -1.3%, on average, in white and gray matter, respectively) and overestimation of T1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored. Reproducibility of the proposed framework is excellent (ΔMPF = -0.03% and ΔT1 = -19.0 ms). The single-point methodology yielded consistent MPF and T1 values with respective maximum relative average bias of -0.15% and -3.5 ms found in white matter. CONCLUSION: The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility.

Simultaneous multi-slice T1 mapping using MOLLI with blipped CAIPIRINHA bSSFP.

BACKGROUND: This study evaluates the possibility for replacing conventional 3 slices, 3 breath-holds MOLLI cardiac T1 mapping with single breath-hold 3 simultaneous multi-slice (SMS3) T1 mapping using blipped-CAIPIRINHA SMS-bSSFP MOLLI sequence. As a major drawback, SMS-bSSFP presents unique artefacts arising from side-lobe slice excitations that are explained by imperfect RF modulation rendering and bSSFP low flip angle enhancement. Amplitude-only RF modulation (AM) is proposed to reduce these artefacts in SMS-MOLLI compared to conventional Wong multi-band RF modulation (WM). MATERIALS AND METHODS: Phantoms and ten healthy volunteers were imaged at 1.5 T using a modified blipped-CAIPIRINHA SMS-bSSFP MOLLI sequence with 3 simultaneous slices. WM-SMS3 and AM-SMS3 were compared to conventional single-slice (SMS1) MOLLI. First, SNR degradation and T1 accuracy were measured in phantoms. Second, artefacts from side-lobe excitations were evaluated in a phantom designed to reproduce fat presence near the heart. Third, the occurrence of these artefacts was observed in volunteers, and their impact on T1 quantification was compared between WM-SMS3 and AM-SMS3 with conventional MOLLI as a reference. RESULTS: In the phantom, larger slice gaps and slice thicknesses yielded higher SNR. There was no significant difference of T1 values between conventional MOLLI and SMS3-MOLLI (both WM and AM). Positive banding artefacts were identified from fat neighbouring the targeted FOV due to side-lobe excitations from WM and the unique bSSFP signal profile. AM RF pulses reduced these artefacts by 38%. In healthy volunteers, AM-SMS3-MOLLI showed similar artefact reduction compared to WM-SMS3-MOLLI (3 ± 2 vs 5 ± 3 corrupted LV segments out of 16). In-vivo native T1 values obtained from conventional MOLLI and AM-SMS3-MOLLI were equivalent in LV myocardium (SMS1-T1 = 935.5 ± 36.1 ms; AM-SMS3-T1 = 933.8 ± 50.2 ms; P = 0.436) and LV blood pool (SMS1-T1 = 1475.4 ± 35.9 ms; AM-SMS3-T1 = 1452.5 ± 70.3 ms; P = 0.515). Identically, no differences were found between SMS1 and SMS3 postcontrast T1 values in the myocardium (SMS1-T1 = 556.0 ± 19.7 ms; SMS3-T1 = 521.3 ± 28.1 ms; P = 0.626) and the blood (SMS1-T1 = 478 ± 65.1 ms; AM-SMS3-T1 = 447.8 ± 81.5; P = 0.085). CONCLUSIONS: Compared to WM RF modulation, AM SMS-bSSFP MOLLI was able to reduce side-lobe artefacts considerably, providing promising results to image the three levels of the heart in a single breath hold. However, few artefacts remained even using AM-SMS-bSSFP due to residual RF imperfections. The proposed blipped-CAIPIRINHA MOLLI T1 mapping sequence provides accurate in vivo T1 quantification in line with those obtained with a single slice acquisition.

Spinal cord and brain tissue impairments as long-term effects of rugby practice? An exploratory study based on T1 and ihMTsat measures.

Rugby players are subject to multiple impacts to their head and neck that could have adverse neurological effects and put them at increased risk of neurodegeneration. Previous studies demonstrated altered default mode network and diffusion metrics on brain, as well as more foraminal stenosis, disc protrusion and neck pain among players of contact sports as compared to healthy controls. However, the long-term effects of practice and repetitive impacts on brain and cervical spinal cord (cSC) of the rugby players have never been systematically investigated. In this study, 15 retired professional and amateur rugby players (R) and 15 age-matched healthy controls (HC) (all males; mean age R: 46.8 ± 7.6; and HC: 48.6 ± 9.5) were recruited both to investigate cord impairments and further characterize brain structure damage. Medical questionnaires including modified Japanese Orthopedic Association scale (mJOA) and Neck Disability Index (NDI) were filled by all participants. A 3 T multi-parametric MR protocol including conventional qualitative techniques such as T1-, T2-, and T2*-weighted sequences, as well as state-of-the art quantitative techniques including MP2RAGE T1 mapping and 3D ihMTRAGE, was used on both brain and cSC. Normalized brain WM and GM volumes, spine Overall Stenosis Score, cord cross-sectional area and regional T1 and ihMT metrics were derived from these acquisitions. Rugby players showed significantly higher NDI scores, as well as a faster decline of normalized brain GM volume with age as compared to HC. Moreover, higher T1 values on cSC suggestive of structural degeneration, together with higher T1 and lower ihMTsat on brain WM suggestive of demyelination, were observed in retired rugby players as compared to age-matched controls, which may suggest cumulative effects of long-term impacts on the tissues. Metrics also suggest early aging and different aging processes on brain tissue in the players. These preliminary observations provide new insights in the domain, which should now be further investigated on larger cohorts and multicentric longitudinal studies, and further correlated to the likelihood of neurodegenerative diseases and risk factors.

A strategy to reduce the sensitivity of inhomogeneous magnetization transfer (ihMT) imaging to radiofrequency transmit field variations at 3 T.

PURPOSE: To minimize the sensitivity of inhomogeneous magnetization transfer gradient-echo (ihMT-GRE) imaging to radiofrequency (RF) transmit field ( B1+ ) inhomogeneities at 3 T. METHODS: The ihMT-GRE sequence was optimized by varying the concentration of the RF saturation energy over time, obtained by increasing the saturation pulse power while extending the sequence repetition time (TR). Different protocols were tested using numerical simulations and human in vivo experiments in the brain white matter (WM) of healthy subjects at 3 T. The sensitivity of the ihMT ratio (ihMTR) to B1+ variations was investigated by comparing measurements obtained at nominal transmitter adjustments and following a 20% global B1+ drop. The resulting relative variations (δihMTR ) were evaluated voxelwise as a function of the local B1+ distribution. The reproducibility of the protocol providing minimal B1+ bias was assessed in a test-retest experiment. RESULTS: In line with simulations, ihMT-GRE experiments conducted at high concentration of the RF energy over time demonstrated strong reduction of the B1+ inhomogeneity effects in the human WM. Under the optimal conditions of 350-ms TR and 3-µT root mean square (RMS) saturation power, 73% of all WM voxels presented δihMTR below 10%. Reproducibility analysis yielded a close-to-zero systematic bias (ΔihMTR = -0.081%) and a high correlation (ρ² = 0.977) between test and retest experiments. CONCLUSION: Concentrating RF saturation energy in ihMT-GRE sequences mitigates the sensitivity of the ihMTR to B1+ variations and allows for clinical-ready ihMT imaging at 3 T. This feature is of particular interest for high and ultra-high field applications.

Cortical inflammation and brain signs of high-risk atherosclerosis in a non-human primate model.

Atherosclerosis is a chronic systemic inflammatory disease, inducing cardiovascular and cerebrovascular acute events. A role of neuroinflammation is suspected, but not yet investigated in the gyrencephalic brain and the related activity at blood-brain interfaces is unknown. A non-human primate model of advanced atherosclerosis was first established using longitudinal blood samples, multimodal imaging and gene analysis in aged animals. Non-human primate carotid lesions were compared with human carotid endarterectomy samples. During the whole-body imaging session, imaging of neuroinflammation and choroid plexus function was performed. Advanced plaques were present in multiple sites, premature deaths occurred and downstream lesions (myocardial fibrosis, lacunar stroke) were present in this model. Vascular lesions were similar to in humans: high plaque activity on PET and MRI imaging and systemic inflammation (high plasma C-reactive protein levels: 42 ± 14 µg/ml). We also found the same gene association (metabolic, inflammatory and anti-inflammatory markers) as in patients with similar histological features. Metabolic imaging localized abnormal brain glucose metabolism in the frontal cortex. It corresponded to cortical neuro-inflammation (PET imaging) that correlated with C-reactive protein level. Multimodal imaging also revealed pronounced choroid plexus function impairment in aging atherosclerotic non-human primates. In conclusion, multimodal whole-body inflammation exploration at the vascular level and blood-brain interfaces identified high-risk aging atherosclerosis. These results open the way for systemic and central inflammation targeting in atherosclerosis in the new era of immunotherapy.

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs.

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.

T1-Based Synthetic Magnetic Resonance Contrasts Improve Multiple Sclerosis and Focal Epilepsy Imaging at 7 T.

OBJECTIVES: Ultra-high field magnetic resonance imaging (MRI) (≥7 T) is a unique opportunity to improve the clinical diagnosis of brain pathologies, such as multiple sclerosis or focal epilepsy. However, several shortcomings of 7 T MRI, such as radiofrequency field inhomogeneities, could degrade image quality and hinder radiological interpretation. To address these challenges, an original synthetic MRI method based on T1 mapping achieved with the magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence was developed. The radiological quality of on-demand T1-based contrasts generated by this technique was evaluated in multiple sclerosis and focal epilepsy imaging at 7 T. MATERIALS AND METHODS: This retrospective study was carried out from October 2017 to September 2019 and included 21 patients with different phenotypes of multiple sclerosis and 35 patients with focal epilepsy who underwent MRI brain examinations using a whole-body investigative 7 T magnetic resonance system. The quality of 2 proposed synthetic contrast images were assessed and compared with conventional images acquired at 7 T using the MP2RAGE sequence by 4 radiologists, evaluating 3 qualitative criteria: signal homogeneity, contrast intensity, and lesion visualization. Statistical analyses were performed on reported quality scores using Wilcoxon rank tests and further multiple comparisons tests. Intraobserver and interobserver reliabilities were calculated as well. RESULTS: Radiological quality scores were reported higher for synthetic images when compared with original images, regardless of contrast, pathologies, or raters considered, with significant differences found for all 3 criteria (P < 0.0001, Wilcoxon rank test). None of the 4 radiologists ever rated a synthetic image "markedly worse" than an original image. Synthetic images were rated slightly less satisfying for only 3 epileptic patients, without precluding lesion identification. CONCLUSION: T1-based synthetic MRI with the MP2RAGE sequence provided on-demand contrasts and high-quality images to the radiologist, facilitating lesion visualization in multiple sclerosis and focal epilepsy, while reducing the magnetic resonance examination total duration by removing an additional sequence.

Comparison of 2D simultaneous multi-slice and 3D GRASE readout schemes for pseudo-continuous arterial spin labeling of cerebral perfusion at 3 T.

OBJECTIVE: In this perfusion magnetic resonance imaging study, the performances of different pseudo-continuous arterial spin labeling (PCASL) sequences were compared: two-dimensional (2D) single-shot readout with simultaneous multislice (SMS), 2D single-shot echo-planar imaging (EPI) and multishot three-dimensional (3D) gradient and spin echo (GRASE) sequences combined with a background-suppression (BS) module. MATERIALS AND METHODS: Whole-brain PCASL images were acquired from seven healthy volunteers. The performance of each protocol was evaluated by extracting regional cerebral blood flow (rCBF) measures using an inline morphometric segmentation prototype. Image data postprocessing and subsequent statistical analyses enabled comparisons at the regional and sub-regional levels. RESULTS: The main findings were as follows: (i) Mean global CBF obtained across methods was were highly correlated, and these correlations were significantly higher among the same readout sequences. (ii) Temporal signal-to-noise ratio and gray-matter-to-white-matter CBF ratio were found to be equivalent for all 2D variants but lower than those of 3D-GRASE. DISCUSSION: Our study demonstrates that the accelerated SMS readout can provide increased acquisition efficiency and/or a higher temporal resolution than conventional 2D and 3D readout sequences. Among all of the methods, 3D-GRASE showed the lowest variability in CBF measurements and thus highest robustness against noise.

PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

In an acute ischaemic stroke, understanding the dynamics of blood-brain barrier injury is of particular importance for the prevention of symptomatic haemorrhagic transformation. However, the available techniques assessing blood-brain barrier permeability are not quantitative and are little used in the context of acute reperfusion therapy. Nanoparticles cross the healthy or impaired blood-brain barrier through combined passive and active processes. Imaging and quantifying their transfer rate could better characterize blood-brain barrier damage and refine the delivery of neuroprotective agents. We previously developed an original endovascular stroke model of acute ischaemic stroke treated by mechanical thrombectomy followed by positron emission tomography-magnetic resonance imaging. Cerebral capillary permeability was quantified for two molecule sizes: small clinical gadolinium Gd-DOTA (<1 nm) and AGuIX® nanoparticles (∼5 nm) used for brain theranostics. On dynamic contrast-enhanced magnetic resonance imaging, the baseline transfer constant K trans was 0.94 [0.48, 1.72] and 0.16 [0.08, 0.33] ×10-3 min-1, respectively, in the normal brain parenchyma, consistent with their respective sizes, and 1.90 [1.23, 3.95] and 2.86 [1.39, 4.52] ×10-3 min-1 in choroid plexus, confirming higher permeability than brain parenchyma. At early reperfusion, K trans for both Gd-DOTA and AGuIX® nanoparticles was significantly higher within the ischaemic area compared to the contralateral hemisphere; 2.23 [1.17, 4.13] and 0.82 [0.46, 1.87] ×10-3 min-1 for Gd-DOTA and AGuIX® nanoparticles, respectively. With AGuIX® nanoparticles, K trans also increased within the ischaemic growth areas, suggesting added value for AGuIX®. Finally, K trans was significantly lower in both the lesion and the choroid plexus in a drug-treated group (ciclosporin A, n = 7) compared to placebo (n = 5). K trans quantification with AGuIX® nanoparticles can monitor early blood-brain barrier damage and treatment effect in ischaemic stroke after reperfusion.

Intravoxel Incoherent Motion at 7 Tesla to quantify human spinal cord perfusion: limitations and promises.

PURPOSE: To develop a noninvasive technique to map human spinal cord (SC) perfusion in vivo. More specifically, to implement an intravoxel incoherent motion (IVIM) protocol at ultrahigh field for the human SC and assess parameters estimation errors. METHODS: Monte-Carlo simulations were conducted to assess estimation errors of 2 standard IVIM fitting approaches (two-step versus one-step fit) over the range of IVIM values reported for the human brain and for typical SC diffusivities. Required signal-to-noise ratio (SNR) was inferred for estimation of the parameters product, fIVIM D* (microvascular fraction times pseudo-diffusion coefficient), within 10% error margins. In-vivo IVIM imaging of the SC was performed at 7T in 6 volunteers. An image processing pipeline is proposed to generate IVIM maps and register them for an atlas-based region-wise analysis. RESULTS: Required b = 0 SNRs for 10% error estimation on fIVIM D* with the one-step fit were 159 and 185 for diffusion-encoding perpendicular and parallel to the SC axis, respectively. Average in vivo b = 0 SNR within cord was 141 ± 79, corresponding to estimation errors of 12.7% and 14.7% according to numerical simulations. Slice- and group-averaging reduced noise in IVIM maps, highlighting the difference in perfusion between gray and white matter. Mean ± standard deviation fIVIM and D* values across subjects within gray (respectively white) matter were 16.0 ± 1.7 (15.0 ± 1.6)% and 11.4 ± 2.9 (11.5 ± 2.4) × 10-3 mm2 /s. CONCLUSION: Single-subject data SNR at 7T was insufficient for reliable perfusion estimation. However, atlas-averaged IVIM maps highlighted the higher microvascular fraction of gray matter compared to white matter, providing first results of healthy human SC perfusion mapping with MRI.

PET [11C]acetate is also a perfusion tracer for kidney evaluation purposes.

RATIONALE: Renal positron emission tomography (PET) functional imaging allows non-invasive and dynamic measurements of functional and metabolic parameters. [15O]H2O is used as a perfusion tracer, and [11C]acetate as an oxidative metabolism in this purpose, requiring two injections to assess those fundamental parameters. Yet, in cardiac physiology study, the high first-pass myocardial extraction fraction of [11C]acetate allowed to use its influx rate as a blood flow marker too. Since [11C]acetate has been characterized by a 20-25% single pass renal extraction in dogs, it could be used as a potential tracer for renal perfusion. The aim of this study was to determine whether [11C]acetate influx rate can be used as quantitative in vivo marker of kidney perfusion in human. METHODS: In 10 healthy subjects, dynamic PET acquisitions were performed after [15O]H2O and [11C]acetate injections spaced by a 15-minute interval. As previously validated, with compartmental modeling of kinetics, renal perfusion and oxidative metabolism were estimated respectively with influx rate of [15O]H2O and efflux rate of [11C]acetate. Additionally, influx rate of [11C]acetate was regressed to influx rate of [15O]H2O. RESULTS: Renal time activity curves of [11C]-acetate was best fitted with a mono compartmental model compared to a bi-compartmental model (p < 0.0001). [11C]acetate influx rate was significantly correlated with perfusion quantified with [15O]H2O (r2 = 0.37, p < 0.001) at baseline. This regression allowed the computation of a renal [11C]acetate extraction fraction (EF), and further the computation of renal blood flow from its influx rate. CONCLUSION: In healthy subjects, over a wide range of renal perfusion, direct estimates of renal oxygen consumption as well as tissue perfusion can be obtained by PET with a single tracer [11C]acetate. This approach needs to be validated in CKD patients, and would be of great interest to design clinical protocol aiming at evaluating ischemic nephropathies candidate to revascularization.

Simultaneous multi-slice cardiac cine with Fourier-encoded self-calibration at 7 Tesla.

PURPOSE: To accelerate cardiac cine at 7 tesla using simultaneous multi-slice (SMS) acquisition with self-calibration to resolve misalignment between calibration and imaging data due to breathing motion. METHODS: A spoiled-gradient echo cine sequence was modified with radiofrequency phase-cycled SMS excitations. A Fourier encoding strategy was applied along the cardiac phase dimension to allow for slice untangling and split-slice GRAPPA calibration. Split-slice GRAPPA was coupled with regular GRAPPA (SMS-GRAPPA) and L1-SPIRiT (SMS-L1SPIRiT) for image reconstruction. 3-slice SMS cine MRI was evaluated in ten subjects against single-slice cine MRI in terms of SNR and contrast-to-noise ratio and slice leakage. RESULTS: SNR decreased significantly from 10.1 ± 7.1 for single-slice cine to 7.4 ± 2.8 for SMS-GRAPPA (P = 0.02) and was recovered to 9.0 ± 4.5 with SMS-L1SPIRiT (P = 0.02). Contrast to noise ratio decreased significantly from 14.5 ± 8.1 for single-slice cine to 5.6 ± 3.6 for SMS-GRAPPA (P < 0.0001) and increased slightly but significantly back to 6.7 ± 4.4 for SMS-L1SPIRiT (P = 0.03). Specific absorption rate restrictions imposed a reduced nominal flip angle (-37 ± 7%, P = 0.02) for 3-slice SMS excitations compared to single-slice acquisitions. SMS slice leakage increased significantly from apex (8.6 ± 6.5 %) to base (13.1 ± 4.1 %, P = 0.03) in the left ventricle. CONCLUSION: Three-fold acceleration of cine at 7T was achieved using the proposed SMS technique. Fourier encoding self-calibration and regularized image reconstruction enabled simultaneous acquisition of three slices without significant SNR decrease but significant CNR decrease linked to the reduced nominal excitation flip angle.

High-resolution 3D diffusion tensor MRI of anesthetized rhesus macaque brain at 3T.

Diffusion Magnetic Resonance Imaging (dMRI) has been widely used to investigate human brain microstructure and connectivity and its abnormalities in a variety of brain deficits, whether acute, neurodevelopmental or neurodegenerative. However, the biological interpretation and validation of dMRI data modelling is still a crucial challenge in the field. In this respect, achieving high spatial resolution in-vivo dMRI in the non-human primate to compare these observations both with human dMRI on the one hand and 'ground truth' microstructural and histological data on the other hand is of outmost importance. Here, we developed a dMRI pulse sequence based on 3D-multishot Echo Planar Imaging (3D-msEPI) on a 3T human clinical scanner. We demonstrate the feasibility of cerebral dMRI at an isotropic resolution of 0.5 mm in 4 anesthetized macaque monkeys. The added value of the high-resolution dMRI is illustrated by focusing on two aspects. First, we show an enhanced descriptive power of the fine substructure of the hippocampus. Second, we show a more physiological description of the interface between cortex grey matter, superficial and deep white matter. Overall, the high spatial resolution dMRI acquisition method proposed in this study is a significant achievement with respect to the state of the art of dMRI on anesthetized monkeys. This study highlights also the potential of very high-resolution dMRI to precisely capture the microstructure of thin cerebral structures such as the hippocampus and superficial white matter.

AGE Content of a Protein Load Is Responsible for Renal Performances: A Pilot Study.

OBJECTIVE: Chronic kidney disease is associated with higher morbidity and mortality in patients with diabetes. A low-protein diet is recommended to slow diabetic nephropathy progression because each protein load leads to renal hemodynamic variations. The aim of our study was to evaluate whether the advanced glycation end products (AGE) content of a protein load is responsible for the protein-induced renal hemodynamic variations in humans. RESEARCH DESIGN AND METHODS: Ten healthy subjects were assigned to a high-protein (1 g/kg) low-AGE (3,000 kU AGE) versus high-AGE (30,000 kU AGE) meal. Renal perfusion, oxygen consumption, and oxygen content were measured before and 120 min after each meal. RESULTS: Renal perfusion (3.2 ± 0.5 vs. 3.8 ± 0.4 mL/min/g; P = 0.0002) and oxygen consumption (0.3 ± 0.04 vs. 0.4 ± 0.08 min-1; P = 0.005) increased significantly after the high-AGE meal compared with the low-AGE meal. CONCLUSIONS: Our results suggest that the AGE content of a protein load is responsible for renal hemodynamic modifications. Therefore, prevention of diabetic nephropathy progression could aim predominantly at reducing food AGE content.

Myocardial arterial spin labeling.

Arterial spin labeling (ASL) is a cardiovascular magnetic resonance (CMR) technique for mapping regional myocardial blood flow. It does not require any contrast agents, is compatible with stress testing, and can be performed repeatedly or even continuously. ASL-CMR has been performed with great success in small-animals, but sensitivity to date has been poor in large animals and humans and remains an active area of research. This review paper summarizes the development of ASL-CMR techniques, current state-of-the-art imaging methods, the latest findings from pre-clinical and clinical studies, and future directions. We also explain how successful developments in brain ASL and small-animal ASL-CMR have helped to inform developments in large animal and human ASL-CMR.

Time course of cardiometabolic alterations in a high fat high sucrose diet mice model and improvement after GLP-1 analog treatment using multimodal cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular complications of obesity and diabetes are major health problems. Assessing their development, their link with ectopic fat deposition and their flexibility with therapeutic intervention is essential. The aim of this study was to longitudinally investigate cardiac alterations and ectopic fat accumulation associated with diet-induced obesity using multimodal cardiovascular magnetic resonance (CMR) in mice. The second objective was to monitor cardiac response to exendin-4 (GLP-1 receptor agonist). METHODS: Male C57BL6R mice subjected to a high fat (35 %) high sucrose (34 %) (HFHSD) or a standard diet (SD) during 4 months were explored every month with multimodal CMR to determine hepatic and myocardial triglyceride content (HTGC, MTGC) using proton MR spectroscopy, cardiac function with cine cardiac MR (CMR) and myocardial perfusion with arterial spin labeling CMR. Furthermore, mice treated with exendin-4 (30 µg/kg SC BID) after 4 months of diet were explored before and 14 days post-treatment with multimodal CMR. RESULTS: HFHSD mice became significantly heavier (+33 %) and displayed glucose homeostasis impairment (1-month) as compared to SD mice, and developed early increase in HTGC (1 month, +59 %) and MTGC (2-month, +63 %). After 3 months, HFHSD mice developed cardiac dysfunction with significantly higher diastolic septum wall thickness (sWtnD) (1.28 ± 0.03 mm vs. 1.12 ± 0.03 mm) and lower cardiac index (0.45 ± 0.06 mL/min/g vs. 0.68 ± 0.07 mL/min/g, p = 0.02) compared to SD mice. A significantly lower cardiac perfusion was also observed (4 months:7.5 ± 0.8 mL/g/min vs. 10.0 ± 0.7 mL/g/min, p = 0.03). Cardiac function at 4 months was negatively correlated to both HTGC and MTGC (p < 0.05). 14-day treatment with Exendin-4 (Ex-4) dramatically reversed all these alterations in comparison with placebo-treated HFHSD. Ex-4 diminished myocardial triglyceride content (-57.8 ± 4.1 %), improved cardiac index (+38.9 ± 10.9 %) and restored myocardial perfusion (+52.8 ± 16.4 %) under isoflurane anesthesia. Interestingly, increased wall thickness and hepatic steatosis reductions were independent of weight loss and glycemia decrease in multivariate analysis (p < 0.05). CONCLUSION: CMR longitudinal follow-up of cardiac consequences of obesity and diabetes showed early accumulation of ectopic fat in mice before the occurrence of microvascular and contractile dysfunction. This study also supports a cardioprotective effect of glucagon-like peptide-1 receptor agonist.

Myocardial perfusion assessment in humans using steady-pulsed arterial spin labeling.

PURPOSE: Although arterial spin labeling (ASL) has become a routinely performed method in the rodent heart, its application to the human heart remains challenged by low tissue blood flow and cardiac and respiratory motion. We hypothesized that an alternative steady-pulsed ASL (spASL) method would provide more efficient perfusion signal averaging by driving the tissue magnetization into a perfusion-dependent steady state. METHODS: We evaluated the feasibility of spASL in the human heart by combining pulsed labeling in the aortic root with a balanced steady state free precession sequence. The spASL scheme was applied to 13 subjects under free breathing. Breathing motion was addressed using retrospective image exclusion based on a contour-based cross-correlation algorithm. RESULTS: The measured signal with spASL was due to labeled blood. We found that the perfusion signal was larger than that obtained with the earlier flow-sensitive alternating inversion recovery (FAIR) method. Averaged myocardial blood flow (MBF) over four myocardial regions was 1.28 ± 0.36 mL·g(-1) ·min(-1) . CONCLUSION: spASL was able to quantify MBF in healthy subjects under free breathing. Because quantification with ASL is more direct than with first-pass perfusion MRI, it appears particularly suited for pathologies with diffuse microvascular alterations, MBF reserve, and follow-up studies.