Multi-band- and in-plane-accelerated diffusion MRI enabled by model-based deep learning in q-space and its extension to learning in the spherical harmonic domain.

PURPOSE: To propose a new method for the recovery of combined in-plane- and multi-band (MB)-accelerated diffusion MRI data. METHODS: Combining MB acceleration with in-plane acceleration is crucial to improve the time efficiency of high (angular and spatial) resolution diffusion scans. However, as the MB factor and in-plane acceleration increase, the reconstruction becomes challenging due to the heavy aliasing. The new reconstruction utilizes an additional q-space prior to constrain the recovery, which is derived from the previously proposed qModeL framework. Specifically, the qModeL prior provides a pre-learned representation of the diffusion signal space to which the measured data belongs. We show that the pre-learned q-space prior along with a model-based iterative reconstruction that accommodate multi-band unaliasing, can efficiently reconstruct the in-plane- and MB-accelerated data. The power of joint reconstruction is maximally utilized by using an incoherent under-sampling pattern in the k-q domain. We tested the proposed method on single- and multi-shell data, with high/low angular resolution, high/low spatial resolution, healthy/abnormal tissues, and 3T/7T field strengths. Furthermore, the learning is extended to the spherical harmonic basis, to provide a rotational invariant learning framework. RESULTS: The qModeL joint reconstruction is shown to simultaneously unalias and jointly recover DWIs with reasonable accuracy in all the cases studied. The reconstruction error from 18-fold accelerated multi-shell datasets was <3%. The microstructural maps derived from the accelerated acquisitions also exhibit reasonable accuracy for both healthy and abnormal tissues. The deep learning (DL)-enabled reconstructions are comparable to those derived using traditional methods. CONCLUSION: qModeL enables the joint recovery of combined in-plane- and MB-accelerated dMRI utilizing DL.

Improved resting state functional connectivity sensitivity and reproducibility using a multiband multi-echo acquisition.

Recent advances in functional MRI techniques include multiband (MB) imaging and multi-echo (ME) imaging. In MB imaging multiple slices are acquired simultaneously leading to significant increases in temporal and spatial resolution. Multi-echo imaging enables multiple echoes to be acquired in one shot, where the ME images can be used to denoise the BOLD time series and increase BOLD sensitivity. In this study, resting state fMRI (rs-fMRI) data were collected using a combined MBME sequence and compared to an MB single echo sequence. In total, 29 subjects were imaged, and 18 of them returned within two weeks for repeat imaging. Participants underwent one MBME scan with three echoes and one MB scan with one echo. Both datasets were processed using standard denoising and advanced denoising. Advanced denoising included multi-echo independent component analysis (ME-ICA) for the MBME data and ICA-AROMA for the MB data. Resting state functional connectivity (RSFC) was evaluated using both selective seed-based and whole grey matter (GM) region-of-interest (ROI) based approaches. The reproducibility of connectivity metrics was also analyzed in the repeat subjects. In addition, functional connectivity density (FCD), a data-driven approach that counts the number of significant connections, both within a local cluster and globally, with each voxel was analyzed. Regardless of the standard or advanced denoising technique, all seed-based RSFC was significantly higher for MBME compared to MB. Much more GM ROI combinations showed significantly higher RSFC for MBME vs. MB. Reproducibility, evaluated using the dice coefficient was significantly higher for MBME relative to MB data. Finally, FCD was also higher for MBME vs. MB data. This study showed higher RSFC for MBME vs. MB data using selected seed-based, whole GM ROI-based, and data-driven approaches. Reproducibility found also higher for MBME data. Taken together, these results indicate that MBME is a promising technique for rs-fMRI.

Split-slice training and hyperparameter tuning of RAKI networks for simultaneous multi-slice reconstruction.

PURPOSE: Simultaneous multi-slice acquisitions are essential for modern neuroimaging research, enabling high temporal resolution functional and high-resolution q-space sampling diffusion acquisitions. Recently, deep learning reconstruction techniques have been introduced for unaliasing these accelerated acquisitions, and robust artificial-neural-networks for k-space interpolation (RAKI) have shown promising capabilities. This study systematically examines the impacts of hyperparameter selections for RAKI networks, and introduces a novel technique for training data generation which is analogous to the split-slice formalism used in slice-GRAPPA. METHODS: RAKI networks were developed with variable hyperparameters and with and without split-slice training data generation. Each network was trained and applied to five different datasets including acquisitions harmonized with Human Connectome Project lifespan protocol. Unaliasing performance was assessed through L1 errors computed between unaliased and calibration frequency-space data. RESULTS: Split-slice training significantly improved network performance in nearly all hyperparameter configurations. Best unaliasing results were achieved with three layer RAKI networks using at least 64 convolutional filters with receptive fields of 7 voxels, 128 single-voxel filters in the penultimate RAKI layer, batch normalization, and no training dropout with the split-slice augmented training dataset. Networks trained without the split-slice technique showed symptoms of network over-fitting. CONCLUSIONS: Split-slice training for simultaneous multi-slice RAKI networks positively impacts network performance. Hyperparameter tuning of such reconstruction networks can lead to further improvements in unaliasing performance.

Multiecho complex total field inversion method (mcTFI) for improved signal modeling in quantitative susceptibility mapping.

PURPOSE: Typical quantitative susceptibility mapping (QSM) reconstruction steps consist of first estimating the magnetization field from the gradient-echo images, and then reconstructing the susceptibility map from the estimated field. The errors from the field-estimation steps may propagate into the final QSM map, and the noise in the estimated field map may no longer be zero-mean Gaussian noise, thus, causing streaking artifacts in the resulting QSM. A multiecho complex total field inversion (mcTFI) method was developed to compute the susceptibility map directly from the multiecho gradient echo images using an improved signal model that retains the Gaussian noise property in the complex domain. It showed improvements in QSM reconstruction over the conventional field-to-source inversion. METHODS: The proposed mcTFI method was compared with the nonlinear total field inversion (nTFI) method in a numerical brain with hemorrhage and calcification, the numerical brains provided by the QSM Challenge 2.0, 18 brains with intracerebral hemorrhage scanned at 3T, and 6 healthy brains scanned at 7T. RESULTS: Compared with nTFI, the proposed mcTFI showed more accurate QSM reconstruction around the lesions in the numerical simulations. The mcTFI reconstructed QSM also showed the best image quality with the least artifacts in the brains with intracerebral hemorrhage scanned at 3T and healthy brains scanned at 7T. CONCLUSION: The proposed multiecho complex total field inversion improved QSM reconstruction over traditional field-to-source inversion through better signal modeling.

Simultaneous multi-slice spin- and gradient-echo dynamic susceptibility-contrast perfusion-weighted MRI of gliomas.

Although combined spin- and gradient-echo (SAGE) dynamic susceptibility-contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T1 -shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo-planar imaging (EPI) sequence with simultaneous multi-slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi-band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR2 *(t) and ΔR2 (t) curves were derived to calculate dynamic signal-to-noise ratio (dSNR), ΔR2 *- and ΔR2 -based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal-appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal-appearing gray matter were not statistically significant between the two protocols. ΔR2 *- and ΔR2 -rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.

Detecting Task Functional MRI Activation Using the Multiband Multiecho (MBME) Echo-Planar Imaging (EPI) Sequence.

BACKGROUND: Blood oxygen level-dependent (BOLD) functional MRI (fMRI) has been widely applied to detect brain activations. Recent advances in multiband (MB) and multiecho (ME) techniques have greatly improved fMRI methods. MB imaging improves temporal and/or spatial resolution, while ME imaging has been shown to improve BOLD sensitivity. This study aimed to evaluate the novel MBME echo planar imaging (EPI) sequence utilizing MB and ME simultaneously to determine if the MBME outperform the MB single echo (MBSE) sequence for task fMRI. PURPOSE: To compare the performance of MBME with MBSE in a task fMRI study. STUDY TYPE: Prospective. POPULATION: A total of 29 healthy volunteers aged 20-46 years (9 male, 20 female). FIELD STRENGTH/SEQUENCE: MBSE and MBME gradient-echo EPI sequences were applied at 3T. Additional T1 -weighted magnetization-prepared rapid acquisition with gradient echo (MPRAGE) was collected. ASSESSMENT: A checkerboard visual task was presented during the functional MBSE and MBME scans. The MBME or MBSE signal was evaluated using the temporal signal-to-noise ratio (tSNR). Task activation was evaluated using the z-score, volume, sensitivity, and specificity. Test-retest metrics of task activation were examined with the Dice coefficient (DC) and intraclass correlation coefficient (ICC) on subjects with repeated scans. STATISTICAL TESTS: A linear mixed-effects model was used to compared MBME and MBSE activation at the voxel base. The paired t-test was used to compare tSNR, activation z-score, and volume, along with sensitivity, specificity, and DC between MBSE and MBME. RESULTS: While similar task activation was detected in the visual cortex, MBME showed higher activation volume and higher sensitivity compared with MBSE (P < 0.05). ICC was higher for MBME than MBSE, while there was a trend of differences in DC (P = 0.08). DATA CONCLUSION: MBME resulted in higher task fMRI activation volume and sensitivity without losing specificity. Reliability was also higher for MBME scans compared with MBSE. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

SMS MUSSELS: A navigator-free reconstruction for simultaneous multi-slice-accelerated multi-shot diffusion weighted imaging.

PURPOSE: To introduce a novel reconstruction method for simultaneous multi-slice (SMS)-accelerated multi-shot diffusion weighted imaging (ms-DWI). METHODS: SMS acceleration using blipped-CAIPI schemes have been proposed to speed up the acquisition of ms-DWIs. The reconstruction of the data requires (a) phase compensation to combine data from different shots and (b) slice unfolding to separate the data of different slices. The traditional approaches first estimate the phase maps corresponding to each shot and slice which are then employed to iteratively recover the slice unfolded DWIs without phase artifacts. In contrast, the proposed reconstruction directly recovers the slice-unfolded k-space data of the multiple shots for each slice in a single-step recovery scheme. The proposed method is enabled by the low-rank property inherent in the k-space samples of ms-DW acquisition. This enabled to formulate a joint recovery scheme that simultaneously (a) unfolds the k-space data of each slice using a SENSE-based scheme and (b) recover the missing k-space samples in each slice of the multi-shot acquisition employing a structured low-rank matrix completion. Additional smoothness regularization is also utilized for higher acceleration factors. The proposed joint recovery is tested on simulated and in vivo data and compared to similar un-navigated methods. RESULTS: Our experiments show effective slice unfolding and successful recovery of DWIs with minimal phase artifacts using the proposed method. The performance is comparable to existing methods at low acceleration factors and better than existing methods for higher acceleration factors. CONCLUSIONS: For the slice accelerations considered in this study, the proposed method can successfully recover DWIs from SMS-accelerated ms-DWI acquisitions.

Exchange kinetics by inversion transfer: integrated analysis of the phosphorus metabolite kinetic exchanges in resting human skeletal muscle at 7 T.

PURPOSE: To develop an inversion pulse-based, chemical exchange saturation transfer-like method for detection of (31) P magnetization exchanges among all nuclear magnetic resonance visible metabolites suitable for providing an integrated kinetic analysis of phosphorus exchange reactions in vivo. METHODS: The exchange kinetics by inversion transfer (EKIT) sequence includes application of a frequency-selective inversion pulse arrayed over the range of relevant (31) P frequencies, followed by a constant delay and a hard readout pulse. A series of EKIT spectra, each given by a plot of Z-magnetization for each metabolite of interest versus frequency of the inversion pulse, can be generated from this single data set. RESULTS: EKIT spectra reflect chemical exchange due to known biochemical reactions, cross-relaxation effects, and relayed magnetization transfers due to both processes. The rate constants derived from EKIT data collected on resting human skeletal muscle were: ATP synthesis via ATP synthase (0.050 ± 0.016 s(-1) ), ATP synthesis via creatine kinase (0.264 ± 0.023 s(-1) ), and cross-relaxation between neighboring spin pairs within ATP (0.164 ± 0.022 s(-1) ). CONCLUSION: EKIT provides a simple, alternative method to detect chemical exchange, cross relaxation, and relayed magnetization transfer effects in human skeletal muscle at 7 T.

Automated High-Order Shimming for Neuroimaging Studies.

B0 inhomogeneity presents a significant challenge in MRI and MR spectroscopy, particularly at high-field strengths, leading to image distortion, signal loss, and spectral broadening. Existing high-order shimming methods can alleviate these issues but often require time-consuming and subjective manual selection of regions of interest (ROIs). To address this, we proposed an automated high-order shimming (autoHOS) method, incorporating deep-learning-based brain extraction and image-based high-order shimming. This approach performs automated real-time brain extraction to define the ROI of the field map to be used in the shimming algorithm. The shimming performance of autoHOS was assessed through in vivo echo-planar imaging (EPI) and spectroscopic studies at both 3T and 7T field strengths. AutoHOS outperforms linear shimming and manual high-order shimming, enhancing both the image and spectral quality by reducing the EPI image distortion and narrowing the MRS spectral lineshapes. Therefore, autoHOS demonstrated a significant improvement in correcting B0 inhomogeneity while eliminating the need for additional user interaction.

Molecular-enriched functional connectivity in the human brain using multiband multi-echo simultaneous ASL/BOLD fMRI.

Receptor-enriched analysis of functional connectivity by targets (REACT) is a strategy to enrich functional MRI (fMRI) data with molecular information on the neurotransmitter distribution density in the human brain, providing a biological basis to the functional connectivity (FC) analysis. Although this approach has been used in BOLD fMRI studies only so far, extending its use to ASL imaging would provide many advantages, including the more direct link of ASL with neuronal activity compared to BOLD and its suitability for pharmacological MRI studies assessing drug effects on baseline brain function. Here, we applied REACT to simultaneous ASL/BOLD resting-state fMRI data of 29 healthy subjects and estimated the ASL and BOLD FC maps related to six molecular systems. We then compared the ASL and BOLD FC maps in terms of spatial similarity, and evaluated and compared the test-retest reproducibility of each modality. We found robust spatial patterns of molecular-enriched FC for both modalities, moderate similarity between BOLD and ASL FC maps and comparable reproducibility for all but one molecular-enriched functional networks. Our findings showed that ASL is as informative as BOLD in detecting functional circuits associated with specific molecular pathways, and that the two modalities may provide complementary information related to these circuits.

Improving the Breath-Holding CVR Measurement Using the Multiband Multi-Echo EPI Sequence.

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is commonly used to measure cerebrovascular reactivity (CVR), which can convey insightful information about neurovascular health. Breath-holding (BH) has been shown to be a practical vasodilatory stimulus for measuring CVR in clinical settings. The conventional BOLD fMRI approach has some limitations, however, such as susceptibility-induced signal dropout at air tissue interfaces and low BOLD sensitivity especially in areas of low T 2 * . These drawbacks can potentially be mitigated with multi-echo sequences, which acquire several images at different echo times in one shot. When combined with multiband techniques, high temporal resolution images can be acquired. This study compared an advanced multiband multi-echo (MBME) echo planar imaging (EPI) sequence with an existing multiband single-echo (MB) sequence to evaluate the repeatability and sensitivity of BH activation and CVR mapping. Images were acquired from 28 healthy volunteers, of which 18 returned for repeat imaging. Both MBME and MB data were pre-processed using both standard and advanced denoising techniques. The MBME data was further processed by combining echoes using a T 2 * -weighted approach and denoising using multi-echo independent component analysis. BH activation was calculated using a general linear model and the respiration response function. CVR was computed as the percent change related to the activation. To account for differences in CVR related to TE, relative CVR (rCVR) was computed and normalized to the mean gray matter CVR. Test-retest metrics were assessed with the Dice coefficient, rCVR difference, within subject coefficient of variation, and the intraclass correlation coefficient. Our findings demonstrate that rCVR for MBME scans were significantly higher than for MB scans across most of the gray matter. In areas of high susceptibility-induced signal dropout, however, MBME rCVR was significantly less than MB rCVR due to artifactually high rCVR for MB scans in these regions. MBME rCVR showed improved test-retest metrics compared with MB. Overall, the MBME sequence displayed superior BOLD sensitivity, improved specificity in areas of signal dropout on MBME scans, enhanced reliability, and reduced variability across subjects compared with MB acquisitions. Our results suggest that the MBME EPI sequence is a promising tool for imaging CVR.

Optimization of hyperparameters for SMS reconstruction.

PURPOSE: Simultaneous multi-slice (SMS) imaging accelerates MRI data acquisition by exciting multiple image slices with a single radiofrequency pulse. Overlapping slices encoded in acquired signal are separated using a mathematical model, which requires estimation of image reconstruction kernels using calibration data. Several parameters used in SMS reconstruction impact the quality and fidelity of final images. Therefore, finding an optimal set of reconstruction parameters is critical to ensure that accelerated acquisition does not significantly degrade resulting image quality. METHODS: Gradient-echo echo planar imaging data were acquired with a range of SMS acceleration factors from a cohort of five volunteers with no known neurological pathology. Images were collected using two available phased-array head coils (a 48-channel array and a reduced diameter 32-channel array) that support SMS. Data from these coils were identically reconstructed offline using a range of coil compression factors and reconstruction kernel parameters. A hybrid space (k-x), externally-calibrated coil-by-coil slice unaliasing approach was used for image reconstruction. The image quality of the resulting reconstructed SMS images was assessed by evaluating correlations with identical echo-planar reference data acquired without SMS. A finger tapping functional MRI (fMRI) experiment was also performed and group analysis results were compared between data sets reconstructed with different coil compression levels. RESULTS: Between the two RF coils tested in this study, the 32-channel coil with smaller dimensions clearly outperformed the larger 48-channel coil in our experiments. Generally, a large calibration region (144-192 samples) and small kernel sizes (2-4 samples) in ky direction improved image quality. Use of regularization in the kernel fitting procedure had a notable impact on the fidelity of reconstructed images and a regularization value 0.0001 provided good image quality. With optimal selection of other hyperparameters in the hybrid space SMS unaliasing algorithm, coil compression caused small reduction in correlation between single-band and SMS unaliased images. Similarly, group analysis of fMRI results did not show a significant influence of coil compression on resulting image quality. CONCLUSIONS: This study demonstrated that the hyperparameters used in SMS reconstruction need to be fine-tuned once the experimental factors such as the RF receive coil and SMS factor have been determined. A cursory evaluation of SMS reconstruction hyperparameter values is therefore recommended before conducting a full-scale quantitative study using SMS technologies.

Quantitative Susceptibility Mapping: MRI at 7T versus 3T.

BACKGROUND AND PURPOSE: Ultrahigh-field 7T promises more than doubling the signal-to-noise ratio (SNR) of 3T for magnetic resonance imaging (MRI), particularly for MRI of magnetic susceptibility effects induced by B0 . Quantitative susceptibility mapping (QSM) is based on deconvolving the induced phase (or field) and would therefore benefit substantially from 7T. The purpose of this work was to compare QSM performance at 7T versus 3T in an intrascanner test-retest experiment with varying echo numbers (5 and 10 echoes). METHODS: A prospective study in N = 10 healthy subjects was carried out at both 3T and 7T field strengths. Gradient echo data using 5 and 10 echoes were acquired twice in each subject. Test-retest reproducibility was assessed using Bland-Altman and regression analysis of region of interest measurements. Image quality was scored by an experienced neuroradiologist. RESULTS: Intrascanner bias was below 3.6 parts-per-billion (ppb) with correlation R2 > .85. Interscanner bias was below 10.9 ppb with correlation R2 > .8. The image quality score for the 3T 10 echo protocol was not different from the 7T 5 echo protocol (P = .65). CONCLUSION: Excellent image quality and good reproducibility was observed. 7T allows equivalent image quality of 3T in half of the scan time.

A phase I study of anti-kinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma.

PURPOSE: Angiogenesis plays an important role in colorectal cancer progression. Stimulation of vascular endothelial growth factor receptor (VEGFR), a transmembrane glycoprotein, results in endothelial mitogenesis. Within this family of receptors, VEGFR 2/kinase-insert-domain-containing receptor (KDR) appear to be principally up-regulated during tumorigenesis. A chimeric anti-KDR antibody, IMC-1C11, blocks VEGFR-KDR interaction and inhibits VEGFR-induced endothelial cell proliferation. This trial seeks to assess the safety, tolerability and feasibility of targeting an important pathway in tumorigenesis. EXPERIMENTAL DESIGN: In a dose-escalation, single-agent study of IMC-1C11, we enrolled 14 patients with colorectal carcinoma and hepatic metastases. Safety-, pharmacokinetic-, immunogenicity-, and magnetic resonance imaging-assessed alteration of vascular effects of IMC-1C11 were evaluated in this trial. IMC-1C11 was infused weekly at 0.2 mg/kg (n = 3), 0.6 mg/kg (n = 4), 2.0 mg/kg (n = 3), and 4.0 mg/kg (n = 4) for 4 weeks, which constituted a cycle. RESULTS: No grade-3 or -4 IMC-1C11-related toxicities were observed. Minor grade-1 bleeding events were observed in four patients [0.2 mg/kg (n = 1) and 0.6 mg/kg (n = 3)]. Each resolved quickly and required no intervention. The starting dose of IMC-1C11 was selected to achieve a C(max) of approximately 5 micro g/ml. This concentration prevented KDR phosphorylation in vitro. Pharmacokinetic analysis demonstrated that the plasma t(1/2) and C(max) were dose dependent with a plasma t(1/2) of 67 +/- 3 h at the 4-mg/kg dose level. Human antichimeric antibodies were detected in 7 of 14 patients. The antibodies to IMC-1C11 inhibited the circulation of the agent in two patients. One patient had prolonged stable disease for seven cycles (28 weeks). The mean changes in tumor-influx volume-transfer constant k(in) (min(-1)) and enhancement factor after 4 weeks of therapy were significantly decreased compared with pretreatment values in 11 patients. CONCLUSION: IMC-1C11 was both safe and well tolerated. Drug levels of IMC-1C11 were reliably predicted. Further clinical investigation of anti-VEGFR/KDR agents is warranted.

In vivo GABA detection with improved selectivity and sensitivity by localized double quantum filter technique at 4.1T.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter for the normal function of mammal and human brain. It is difficult to detect GABA signal with the conventional single quantum technique due to its relatively low concentration and overlapping with other signals from creatine (Cr), glutathione (GSH), as well as macromolecules. Using a high-selective read pulse, DANTE, and at the facility of increased sensitivity and chemical shift resolution at high-field 4.1T, GABA editing by double quantum filter (DQF) with robust suppression of Cr and GSH was achieved. Our editing efficiency of 40-50% was achievable on a GABA phantom (50 mM GABA and 61 mM choline). Furthermore, GABA editing spectra were acquired with echo time TE = 77 ms, and any possible macromolecular contamination to GABA editing spectra was found to be negligible. This high-field DQF setup was applied to 11 healthy volunteers, and the mean GABA level was measured to be 1.12 +/- 0.15 mM in the occipital lobe in reference to 7.1 mM Cr concentration.