Robust multishot diffusion-weighted imaging of the abdomen with region-based shot rejection.

PURPOSE: Diffusion-weighted (DW) imaging provides a useful clinical contrast, but is susceptible to motion-induced dephasing caused by the application of strong diffusion gradients. Phase navigators are commonly used to resolve shot-to-shot motion-induced phase in multishot reconstructions, but poor phase estimates result in signal dropout and Apparent Diffusion Coefficient (ADC) overestimation. These artifacts are prominent in the abdomen, a region prone to involuntary cardiac and respiratory motion. To improve the robustness of DW imaging in the abdomen, region-based shot rejection schemes that selectively weight regions where the shot-to-shot phase is poorly estimated were evaluated. METHODS: Spatially varying weights for each shot, reflecting both the accuracy of the estimated phase and the degree of subvoxel dephasing, were estimated from the phase navigator magnitude images. The weighting was integrated into a multishot reconstruction using different formulations and phase navigator resolutions and tested with different phase navigator resolutions in multishot DW-echo Planar Imaging acquisitions of the liver and pancreas, using conventional monopolar and velocity-compensated diffusion encoding. Reconstructed images and ADC estimates were compared qualitatively. RESULTS: The proposed region-based shot rejection reduces banding and signal dropout artifacts caused by physiological motion in the liver and pancreas. Shot rejection allows conventional monopolar diffusion encoding to achieve median ADCs in the pancreas comparable to motion-compensated diffusion encoding, albeit with a greater spread of ADCs. CONCLUSION: Region-based shot rejection is a linear reconstruction that improves the motion robustness of multi-shot DWI and requires no sequence modifications.

Comprehensive assessment of nonuniform image quality: Application to imaging near metal.

PURPOSE: Comprehensive assessment of image quality requires accounting for spatial variations in (i) intensity artifact, (ii) geometric distortion, (iii) signal-to-noise ratio (SNR), and (iv) spatial resolution, among other factors. This work presents an ensemble of methods to meet this need, from phantom design to image analysis, and applies it to the scenario of imaging near metal. METHODS: A modular phantom design employing a gyroid lattice is developed to enable the co-registered volumetric quantitation of image quality near a metallic hip implant. A method for measuring spatial resolution by means of local point spread function (PSF) estimation is presented and the relative fitness of gyroid and cubic lattices is examined. Intensity artifact, geometric distortion, and SNR maps are also computed. Results are demonstrated with 2D-FSE and MAVRIC-SL scan protocols on a 3T MRI scanner. RESULTS: The spatial resolution method demonstrates a worst-case error of 0.17 pixels for measuring in-plane blurring up to 3 pixels (full width at half maximum). The gyroid outperforms a cubic lattice design for the local PSF estimation task. The phantom supports four configurations toggling the presence/absence of both metal and structure with good spatial correspondence for co-registered analysis of the four quality factors. The marginal scan time to evaluate one scan protocol amounts to five repetitions. The phantom design can be fabricated in 2 days at negligible material cost. CONCLUSION: The phantom and associated analysis methods can elucidate complex image quality trade-offs involving intensity artifact, geometric distortion, SNR, and spatial resolution. The ensemble of methods is suitable for benchmarking imaging performance near metal.

Distortion-free water-fat separated diffusion-weighted imaging using spatiotemporal joint reconstruction.

PURPOSE: Diffusion-weighted imaging (DWI) suffers from geometric distortion and chemical shift artifacts due to the commonly used Echo Planar Imaging (EPI) trajectory. Even with fat suppression in DWI, severe B0 and B1 variations can result in residual fat, which becomes both a source of image artifacts and a confounding factor in diffusion-weighted contrast in distinguishing benign and malignant tissues. This work presents a method for acquiring distortion-free diffusion-weighted images using spatiotemporal acquisition and joint reconstruction. Water-fat separation is performed by chemical-shift encoding. METHODS: Spatiotemporal acquisition is employed to obtain distortion-free images at a series of echo times. Chemical-shift encoding is used for water-fat separation. Reconstruction and separation are performed jointly in the spat-spectral domain. To address the shot-to-shot motion-induced phase in DWI, an Fast Spin Echo (FSE)-based phase navigator is incorporated into the sequence to obtain distortion-free phase information. The proposed method was validated in phantoms and in vivo for the brain, head and neck, and breast. RESULTS: The proposed method enables the acquisition of distortion-free diffusion-weighted images in the presence of B0 field inhomogenieties commonly observed in the body. Water and fat components are separated with no obvious spectral leakage artifacts. The estimated Apparent Diffusion Coefficient (ADC) is comparable to that of multishot DW-EPI. CONCLUSION: Distortion-free, water-fat separated diffusion-weighted images in body can be obtained through the utilization of spatiotemporal acquisition and joint reconstruction methods.

A diffusion-prepared reduced FOV sequence for prostate MRI near metallic implants.

PURPOSE: To enable diffusion weighted imaging in prostate patients with metallic total hip replacements in clinically feasible scan times for prostate cancer screening, and avoid distortion and dropout artifacts present in the conventionally used Echo Planar Imaging (EPI). METHODS: A reduced field of view (FOV) diffusion-prepared sequence that is robust to the B 0 $$ {\kern0em }_0 $$ inhomogeneities produced by total hip replacements was achieved using high radiofrequency (RF) bandwidth pulses and manipulation for stimulated echo pathways. The reduced FOV along the A/P direction was obtained using slice-select gradient reversal, and the prepared magnetization was imaged with a three-dimensional RF-spoiled gradient echo readout. The sequence was validated in phantom experiments, in vivo in healthy volunteers with and without total hip replacements, and in vivo in patients undergoing a standard MRI prostate exam. RESULTS: The proposed sequence is robust to shading and distortion artifacts that are encountered by standard diffusion-weighted EPI in the presence of moderate off-resonance. Apparent diffusion coefficient estimates obtained by the proposed sequence were comparable to those obtained with diffusion-weighted EPI. CONCLUSION: Acquisition of distortionless diffusion weighted images of the prostate is feasible in patients with total hip replacements on conventional, whole-body 3T MRI, using a b-value of 800 s / mm 2 $$ \mathrm{s}/{\mathrm{mm}}^2 $$ and nominal resolution of 1.7 × $$ \times $$ 1.7 × $$ \times $$ 4 mm3 in scan times of 6 min.

Distortionless, free-breathing, and respiratory resolved 3D diffusion weighted imaging of the abdomen.

PURPOSE: Abdominal imaging is frequently performed with breath holds or respiratory triggering to reduce the effects of respiratory motion. Diffusion weighted sequences provide a useful clinical contrast but have prolonged scan times due to low signal-to-noise ratio (SNR), and cannot be completed in a single breath hold. Echo-planar imaging (EPI) is the most commonly used trajectory for diffusion weighted imaging but it is susceptible to off-resonance artifacts. A respiratory resolved, three-dimensional (3D) diffusion prepared sequence that obtains distortionless diffusion weighted images during free-breathing is presented. Techniques to address the myriad of challenges including: 3D shot-to-shot phase correction, respiratory binning, diffusion encoding during free-breathing, and robustness to off-resonance are described. METHODS: A twice-refocused, M1-nulled diffusion preparation was combined with an RF-spoiled gradient echo readout and respiratory resolved reconstruction to obtain free-breathing diffusion weighted images in the abdomen. Cartesian sampling permits a sampling density that enables 3D shot-to-shot phase navigation and reduction of transient fat artifacts. Theoretical properties of a region-based shot rejection are described. The region-based shot rejection method was evaluated with free-breathing (normal and exaggerated breathing), and respiratory triggering. The proposed sequence was compared in vivo with multishot DW-EPI. RESULTS: The proposed sequence exhibits no evident distortion in vivo when compared to multishot DW-EPI, robustness to B0 and B1 field inhomogeneities, and robustness to motion from different respiratory patterns. CONCLUSION: Acquisition of distortionless, diffusion weighted images is feasible during free-breathing with a b-value of 500 s/mm2, scan time of 6 min, and a clinically viable reconstruction time.

Hyperpolarized 13 C metabolic imaging of the human abdomen with spatiotemporal denoising.

PURPOSE: Improving the quality and maintaining the fidelity of large coverage abdominal hyperpolarized (HP) 13 C MRI studies with a patch based global-local higher-order singular value decomposition (GL-HOVSD) spatiotemporal denoising approach. METHODS: Denoising performance was first evaluated using the simulated [1-13 C]pyruvate dynamics at different noise levels to determine optimal kglobal and klocal parameters. The GL-HOSVD spatiotemporal denoising method with the optimized parameters was then applied to two HP [1-13 C]pyruvate EPI abdominal human cohorts (n = 7 healthy volunteers and n = 8 pancreatic cancer patients). RESULTS: The parameterization of kglobal = 0.2 and klocal = 0.9 denoises abdominal HP data while retaining image fidelity when evaluated by RMSE. The kPX (conversion rate of pyruvate-to-metabolite, X = lactate or alanine) difference was shown to be <20% with respect to ground-truth metabolic conversion rates when there is adequate SNR (SNRAUC > 5) for downstream metabolites. In both human cohorts, there was a greater than nine-fold gain in peak [1-13 C]pyruvate, [1-13 C]lactate, and [1-13 C]alanine apparent SNRAUC . The improvement in metabolite SNR enabled a more robust quantification of kPL and kPA . After denoising, we observed a 2.1 ± 0.4 and 4.8 ± 2.5-fold increase in the number of voxels reliably fit across abdominal FOVs for kPL and kPA quantification maps. CONCLUSION: Spatiotemporal denoising greatly improves visualization of low SNR metabolites particularly [1-13 C]alanine and quantification of [1-13 C]pyruvate metabolism in large FOV HP 13 C MRI studies of the human abdomen.

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage.

Hyperpolarized (HP) 13C Magnetic Resonance Imaging (MRI) was applied for the first time to image and quantify the uptake and metabolism of [2-13C]pyruvate in the human brain to provide new metabolic information on cerebral energy metabolism. HP [2-13C]pyruvate was injected intravenously and imaged in 5 healthy human volunteer exams with whole brain coverage in a 1-minute acquisition using a specialized spectral-spatial multi-slice echoplanar imaging (EPI) pulse sequence to acquire 13C-labeled volumetric and dynamic images of [2-13C]pyruvate and downstream metabolites [5-13C]glutamate and [2-13C]lactate. Metabolic ratios and apparent conversion rates of pyruvate-to-lactate (kPL) and pyruvate-to-glutamate (kPG) were quantified to investigate simultaneously glycolytic and oxidative metabolism in a single injection.

Hyperpolarized 13 C Metabolic MRI of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related death in the United States. However, early response assessment using the current approach of measuring changes in tumor size on computed tomography (CT) or MRI is challenging. PURPOSE: To investigate the feasibility of hyperpolarized (HP) [1-13 C]pyruvate MRI to quantify metabolism in the normal appearing pancreas and PDA, and to assess changes in PDA metabolism following systemic chemotherapy. STUDY TYPE: Prospective. SUBJECTS: Six patients (65.0 ± 7.6 years, 2 females) with locally advanced or metastatic PDA enrolled prior to starting a new line of systemic chemotherapy. FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted gradient echo, metabolite-selective 13 C echoplanar imaging. ASSESSMENT: Time-resolved HP [1-13 C]pyruvate data were acquired before (N = 6) and 4-weeks after (N = 3) treatment initiation. Pyruvate metabolism, as quantified by pharmacokinetic modeling and metabolite area-under-the-curve ratios, was assessed in manually segmented PDA and normal appearing pancreas ROIs (N = 5). The change in tumor metabolism before and 4-weeks after treatment initiation was assessed in primary PDA (N = 2) and liver metastases (N = 1), and was compared to objective tumor response defined by response evaluation criteria in solid tumors (RECIST) on subsequent CTs. STATISTICAL TESTS: Descriptive tests (mean ± standard deviation), model fit error for pharmacokinetic rate constants. RESULTS: Primary PDA showed reduced alanine-to-lactate ratios when compared to normal pancreas, due to increased lactate-to-pyruvate or reduced alanine-to-pyruvate ratios. Of the three patients who received HP [1-13 C]pyruvate MRI before and 4-weeks after treatment initiation, one patient had a primary tumor with early metabolic response (increase in alanine-to-lactate) and subsequent partial response according to RECIST, one patient had a primary tumor with relatively stable metabolism and subsequent stable disease by RECIST, and one patient had metastatic PDA with increase in lactate-to-pyruvate of the liver metastases and corresponding progressive disease according to RECIST. DATA CONCLUSION: Altered pyruvate metabolism with increased lactate or reduced alanine was observed in the primary tumor. Early metabolic response assessed at 4-weeks after treatment initiation correlated with subsequent objective tumor response assessed using RECIST. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Energizing Mitochondria to Prevent Mobility Loss in Aging: Rationale and Hypotheses.

Based on recent studies from our group and others, we hypothesize that mitochondrial dysfunction during aging may be the root cause of mobility decline through deficits in the musculoskeletal and central nervous systems. Mitochondrial dysfunction could be a therapeutic target to prevent mobility decline in aging.

The role of the bladder diary in phenotyping men with LUTS.

AIMS: The aim of this study was to compare the clinical characteristics of men with lower urinary tract symptoms (LUTS) grouped by 24-h urine output determined from a bladder voiding diary. METHODS: An online database was queried to identify men who completed a 24-hour bladder diary (24HBD), and the Lower Urinary Tract Symptom Score (LUTSS) questionnaire from 2015 to 2019 using a mobile app. Data from the bladder diary and questionnaire were contemporaneously matched within a 2-week period. Additional data, including maximum uroflow (Qmax ) and postvoid residual urine (PVR), were obtained from the electronic medical record (EMR). The cohort was divided into three groups: normal, oliguria, and polyuria based on their 24-hour voided volume (24HVV). The LUTSS, 24HVV, maximum voided volume (MVV), maximum flow rate (Qmax ), and PVR were compared between those with oliguria and polyuria. RESULTS: A total of 327 men (mean age 62, SD: 19) completed the LUTSS questionnaire and contemporaneous 24HBD. Of these, 61% had a normal 24HVV, 13% had oliguria, and 26% had polyuria. A total of 147 patients from the study cohort had contemporaneous Qmax and PVR abstracted from the EMR. There was no difference in symptom severity, bother, or PVR among the three patient groups. However, several objective metrics were significantly correlated with urine output. Men with oliguria, as compared to men with polyuria were older (65 vs. 55 years) and had lower MVV (260 vs. 470 mL), fewer voids/24 h (8 vs. 13), and lower Qmax (8.5 vs. 18.3 mL/s). CONCLUSIONS: These observations suggest that men with oliguria or polyuria and LUTS constitute easily distinguished phenotypes that might require different diagnostic and therapeutic algorithms. Those with oliguria were older, and had lower MVVs and much lower uroflows, suggesting that they are more likely to have underlying disorders such as bladder outlet obstruction and detrusor underactivity or may be patients with overactive bladder who reduced fluid intake to improve symptoms.

A joint linear reconstruction for multishot diffusion weighted non-Carr-Purcell-Meiboom-Gill fast spin echo with full signal.

PURPOSE: Diffusion weighted Fast Spin Echo (DW-FSE) is a promising approach for distortionless DW imaging that is robust to system imperfections such as eddy currents and off-resonance. Due to non-Carr-Purcell-Meiboom-Gill (CPMG) magnetization, most DW-FSE sequences discard a large fraction of the signal ( 2 - 2 × $$ \sqrt{2}-2\times $$ ), reducing signal-to-noise ratio (SNR) efficiency compared to DW-EPI. The full FSE signal can be preserved by quadratically incrementing the transmit phase of the refocusing pulses, but this method of resolving non-CPMG magnetization has only been applied to single-shot DW-FSE due to challenges associated with image reconstruction. We present a joint linear reconstruction for multishot quadratic phase increment data that addresses these challenges and corrects ghosting from both shot-to-shot phase and intrashot signal oscillations. Multishot imaging reduces T2 blur and joint reconstruction of shots improves g-factor performance. A thorough analysis on the condition number of the proposed linear system is described. METHODS: A joint multishot reconstruction is derived from the non-CPMG signal model. Multishot quadratic phase increment DW-FSE was tested in a standardized diffusion phantom and compared to single-shot DW-FSE and DW-EPI in vivo in the brain, cervical spine, and prostate. The pseudo multiple replica technique was applied to generate g-factor and SNR maps. RESULTS: The proposed joint shot reconstruction eliminates ghosting from shot-to-shot phase and intrashot oscillations. g-factor performance is improved compared to previously proposed reconstructions, permitting efficient multishot imaging. apparent diffusion coefficient estimates in phantom experiments and in vivo are comparable to those obtained with conventional methods. CONCLUSION: Multi-shot non-CPMG DW-FSE data with full signal can be jointly reconstructed using a linear model.

Volumetric and multispectral DWI near metallic implants using a non-linear phase Carr-Purcell-Meiboom-Gill diffusion preparation.

PURPOSE: DWI near metal implants has not been widely explored due to substantial challenges associated with through-slice and in-plane distortions, the increased encoding requirement of different spectral bins, and limited SNR. There is no widely adopted clinical protocol for DWI near metal since the commonly used EPI trajectory fails completely due to distortion from extreme off-resonance ranging from 2 to 20 kHz. We present a sequence that achieves DWI near metal with moderate b-values (400-500 s/mm2 ) and volumetric coverage in clinically feasible scan times. THEORY AND METHODS: Multispectral excitation with Cartesian sampling, view angle tilting, and kz phase encoding reduce in-plane and through-plane off-resonance artifacts, and Carr-Purcell-Meiboom-Gill (CPMG) spin-echo refocusing trains counteract T2* effects. The effect of random phase on the refocusing train is eliminated using a stimulated echo diffusion preparation. Root-flipped Shinnar-Le Roux refocusing pulses permits preparation of a high spectral bandwidth, which improves imaging times by reducing the number of excitations required to cover the desired spectral range. B1 sensitivity is reduced by using an excitation that satisfies the CPMG condition in the preparation. A method for ADC quantification insensitive to background gradients is presented. RESULTS: Non-linear phase refocusing pulses reduces the peak B1 by 46% which allows RF bandwidth to be doubled. Simulations and phantom experiments show that a non-linear phase CPMG pulse pair reduces B1 sensitivity. Application in vivo demonstrates complementary contrast to conventional multispectral acquisitions and improved visualization compared to DW-EPI. CONCLUSION: Volumetric and multispectral DW imaging near metal can be achieved with a 3D encoded sequence.

Circumventing the curse of dimensionality in magnetic resonance fingerprinting through a deep learning approach.

Magnetic resonance fingerprinting (MRF) is a rapidly developing approach for fast quantitative MRI. A typical drawback of dictionary-based MRF is an explosion of the dictionary size as a function of the number of reconstructed parameters, according to the "curse of dimensionality", which determines an explosion of resource requirements. Neural networks (NNs) have been proposed as a feasible alternative, but this approach is still in its infancy. In this work, we design a deep learning approach to MRF using a fully connected network (FCN). In the first part we investigate, by means of simulations, how the NN performance scales with the number of parameters to be retrieved in comparison with the standard dictionary approach. Four MRF sequences were considered: IR-FISP, bSSFP, IR-FISP-B1 , and IR-bSSFP-B1 , the latter two designed to be more specific for B1+ parameter encoding. Estimation accuracy, memory usage, and computational time required to perform the estimation task were considered to compare the scalability capabilities of the dictionary-based and the NN approaches. In the second part we study optimal training procedures by including different data augmentation and preprocessing strategies during training to achieve better accuracy and robustness to noise and undersampling artifacts. The study is conducted using the IR-FISP MRF sequence exploiting both simulations and in vivo acquisitions. Results demonstrate that the NN approach outperforms the dictionary-based approach in terms of scalability capabilities. Results also allow us to heuristically determine the optimal training strategy to make an FCN able to predict T1 , T2 , and M0 maps that are in good agreement with those obtained with the original dictionary approach. k-SVD denoising is proposed and found to be critical as a preprocessing step to handle undersampled data.

Whole-Abdomen Metabolic Imaging of Healthy Volunteers Using Hyperpolarized [1-13 C]pyruvate MRI.

BACKGROUND: Hyperpolarized 13 C MRI quantitatively measures enzyme-catalyzed metabolism in cancer and metabolic diseases. Whole-abdomen imaging will permit dynamic metabolic imaging of several abdominal organs simultaneously in healthy and diseased subjects. PURPOSE: Image hyperpolarized [1-13 C]pyruvate and products in the abdomens of healthy volunteers, overcoming challenges of motion, magnetic field variations, and spatial coverage. Compare hyperpolarized [1-13 C]pyruvate metabolism across abdominal organs of healthy volunteers. STUDY TYPE: Prospective technical development. SUBJECTS: A total of 13 healthy volunteers (8 male), 21-64 years (median 36). FIELD STRENGTH/SEQUENCE: A 3 T. Proton: T1 -weighted spoiled gradient echo, T2 -weighted single-shot fast spin echo, multiecho fat/water imaging. Carbon-13: echo-planar spectroscopic imaging, metabolite-specific echo-planar imaging. ASSESSMENT: Transmit magnetic field was measured. Variations in main magnetic field (ΔB0 ) determined using multiecho proton acquisitions were compared to carbon-13 acquisitions. Changes in ΔB0 were measured after localized shimming. Improvements in metabolite signal-to-noise ratio were calculated. Whole-organ regions of interests were drawn over the liver, spleen, pancreas, and kidneys by a single investigator. Metabolite signals, time-to-peak, decay times, and mean first-order rate constants for pyruvate-to-lactate (kPL ) and alanine (kPA ) conversion were measured in each organ. STATISTICAL TESTS: Linear regression, one-sample Kolmogorov-Smirnov tests, paired t-tests, one-way ANOVA, Tukey's multiple comparisons tests. P ≤ 0.05 considered statistically significant. RESULTS: Proton ΔB0 maps correlated with carbon-13 ΔB0 maps (slope = 0.93, y-intercept = -2.88, R2  = 0.73). Localized shimming resulted in mean frequency offset within ±25 Hz for all organs. Metabolite SNR significantly increased after denoising. Mean kPL and kPA were highest in liver, followed by pancreas, spleen, and kidneys (all comparisons with liver were significant). DATA CONCLUSION: Whole-abdomen coverage with hyperpolarized carbon-13 MRI was feasible despite technical challenges. Multiecho gradient echo 1 H acquisitions accurately predicted chemical shifts observed using carbon-13 spectroscopy. Carbon-13 acquisitions benefited from local shimming. Metabolite energetics in the abdomen compiled for healthy volunteers can be used to design larger clinical trials in patients with metabolic diseases. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Hyperpolarized carbon 13 MRI in liver diseases: Recent advances and future opportunities.

Hyperpolarized carbon-13 magnetic resonance imaging (HP 13 C MRI) is a recently translated metabolic imaging technique. With dissolution dynamic nuclear polarization (d-DNP), more than 10 000-fold signal enhancement can be readily reached, making it possible to visualize real-time metabolism and specific substrate-to-metabolite conversions in the liver after injecting carbon-13 labelled probes. Increasing evidence suggests that HP 13 C MRI is a potential tool in detecting liver abnormalities, predicting disease progression and monitoring response treatment. In this review, we will introduce the recent progresses of HP 13 C MRI in diffuse liver diseases and liver malignancies and discuss its future opportunities from a clinical perspective, hoping to provide a comprehensive overview of this novel technique in liver diseases and highlight its scientific and clinical potential in the field of hepatology.

Monkeypox in a Young Infant - Florida, 2022.

In August 2022, the Florida Department of Health (FDOH) was notified of a suspected case of monkeypox in an infant aged <2 months who was admitted to a Florida hospital with a rash and cellulitis. This case report highlights findings from the related epidemiologic investigation and describes the public health actions taken. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* This is the youngest patient with confirmed monkeypox infection in Florida to date.

Monkeypox Virus Infection Resulting from an Occupational Needlestick - Florida, 2022.

In August 2022, the Florida Department of Health notified CDC of a nurse who acquired monkeypox through an occupational exposure while providing care to a patient with monkeypox. To date, occupationally acquired Monkeypox virus (MPXV) infections in health care personnel (HCP) have been rarely reported during the 2022 multinational outbreak (1,2). This report describes the first reported U.S. case and recommends approaches for preventing occupationally acquired MPXV infections in HCP.

IDL-PPBopt: A Strategy for Prediction and Optimization of Human Plasma Protein Binding of Compounds via an Interpretable Deep Learning Method.

The prediction and optimization of pharmacokinetic properties are essential in lead optimization. Traditional strategies mainly depend on the empirical chemical rules from medicinal chemists. However, with the rising amount of data, it is getting more difficult to manually extract useful medicinal chemistry knowledge. To this end, we introduced IDL-PPBopt, a computational strategy for predicting and optimizing the plasma protein binding (PPB) property based on an interpretable deep learning method. At first, a curated PPB data set was used to construct an interpretable deep learning model, which showed excellent predictive performance with a root mean squared error of 0.112 for the entire test set. Then, we designed a detection protocol based on the model and Wilcoxon test to identify the PPB-related substructures (named privileged substructures, PSubs) for each molecule. In total, 22 general privileged substructures (GPSubs) were identified, which shared some common features such as nitrogen-containing groups, diamines with two carbon units, and azetidine. Furthermore, a series of second-level chemical rules for each GPSub were derived through a statistical test and then summarized into substructure pairs. We demonstrated that these substructure pairs were equally applicable outside the training set and accordingly customized the structural modification schemes for each GPSub, which provided alternatives for the optimization of the PPB property. Therefore, IDL-PPBopt provides a promising scheme for the prediction and optimization of the PPB property and would be helpful for lead optimization of other pharmacokinetic properties.

Clinical utility of accelerated MAVRIC-SL with robust-PCA compared to conventional MAVRIC-SL in evaluation of total hip arthroplasties.

OBJECTIVE: To compare the diagnostic performance of a conventional metal artifact suppression sequence MAVRIC-SL (multi-acquisition variable-resonance image combination selective) and a novel 2.6-fold faster sequence employing robust principal component analysis (RPCA), in the MR evaluation of hip implants at 3 T. MATERIALS AND METHODS: Thirty-six total hip implants in 25 patients were scanned at 3 T using a conventional MAVRIC-SL proton density-weighted sequence and an RPCA MAVRIC-SL proton density-weighted sequence. Comparison was made of image quality, geometric distortion, visualization around acetabular and femoral components, and conspicuity of abnormal imaging findings using the Wilcoxon signed-rank test and a non-inferiority test. Abnormal findings were correlated with subsequent clinical management and intraoperative findings if the patient underwent subsequent surgery. RESULTS: Mean scores for conventional MAVRIC-SL were better than RPCA MAVRIC-SL for all qualitative parameters (p < 0.05), although the probability of RPCA MAVRIC-SL being clinically useful was non-inferior to conventional MAVRIC-SL (within our accepted 10% difference, p < 0.05), except for visualization around the acetabular component. Abnormal imaging findings were seen in 25 hips, and either equally visible or visible but less conspicuous on RPCA MAVRIC-SL in 21 out of 25 cases. In 4 cases, a small joint effusion was queried on MAVRIC-SL but not RPCA MAVRIC-SL, but the presence or absence of a small effusion did not affect subsequent clinical management and patient outcome. CONCLUSION: While the overall image quality is reduced, RPCA MAVRIC-SL allows for significantly reduced scan time and maintains almost equal diagnostic performance.

Specialized computational methods for denoising, B1 correction, and kinetic modeling in hyperpolarized 13 C MR EPSI studies of liver tumors.

PURPOSE: To develop a novel post-processing pipeline for hyperpolarized (HP) 13 C MRSI that integrates tensor denoising and B1+ correction to measure pyruvate-to-lactate conversion rates (kPL ) in patients with liver tumors. METHODS: Seven HP 13 C MR scans of progressing liver tumors were acquired using a custom 13 C surface transmit/receive coil and the echo-planar spectroscopic imaging (EPSI) data analysis included B0 correction, tensor rank truncation, and zero- and first-order phase corrections to recover metabolite signals that would otherwise be obscured by spectral noise as well as a correction for inhomogeneous transmit ( B1+ ) using a B1+ map aligned to the coil position for each patient scan. Processed HP data and corrected flip angles were analyzed with an inputless two-site exchange model to calculate kPL . RESULTS: Denoising averages SNR increases of pyruvate, lactate, and alanine were 37.4-, 34.0-, and 20.1-fold, respectively, with lactate and alanine dynamics most noticeably recovered and better defined. In agreement with Monte Carlo simulations, over-flipped regions underestimated kPL and under-flipped regions overestimated kPL . B1+ correction addressed this issue. CONCLUSION: The new HP 13 C EPSI post-processing pipeline integrated tensor denoising and B1+ correction to measure kPL in patients with liver tumors. These technical developments not only recovered metabolite signals in voxels that did not receive the prescribed flip angle, but also increased the extent and accuracy of kPL estimations throughout the tumor and adjacent regions including normal-appearing tissue and additional lesions.