TCRs are randomly distributed on the plasma membrane of resting antigen-experienced T cells.

The main function of T cells is to identify harmful antigens as quickly and precisely as possible. Super-resolution microscopy data have indicated that global clustering of T cell antigen receptors (TCRs) occurs before T cell activation. Such pre-activation clustering has been interpreted as representing a potential regulatory mechanism that fine tunes the T cell response. We found here that apparent TCR nanoclustering could be attributed to overcounting artifacts inherent to single-molecule-localization microscopy. Using complementary super-resolution approaches and statistical image analysis, we found no indication of global nanoclustering of TCRs on antigen-experienced CD4+ T cells under non-activating conditions. We also used extensive simulations of super-resolution images to provide quantitative limits for the degree of randomness of the TCR distribution. Together our results suggest that the distribution of TCRs on the plasma membrane is optimized for fast recognition of antigen in the first phase of T cell activation.

Dark-field computed tomography reaches the human scale.

X-ray computed tomography (CT) is one of the most commonly used three-dimensional medical imaging modalities today. It has been refined over several decades, with the most recent innovations including dual-energy and spectral photon-counting technologies. Nevertheless, it has been discovered that wave-optical contrast mechanisms-beyond the presently used X-ray attenuation-offer the potential of complementary information, particularly on otherwise unresolved tissue microstructure. One such approach is dark-field imaging, which has recently been introduced and already demonstrated significantly improved radiological benefit in small-animal models, especially for lung diseases. Until now, however, dark-field CT could not yet be translated to the human scale and has been restricted to benchtop and small-animal systems, with scan durations of several minutes or more. This is mainly because the adaption and upscaling to the mechanical complexity, speed, and size of a human CT scanner so far remained an unsolved challenge. Here, we now report the successful integration of a Talbot-Lau interferometer into a clinical CT gantry and present dark-field CT results of a human-sized anthropomorphic body phantom, reconstructed from a single rotation scan performed in 1 s. Moreover, we present our key hardware and software solutions to the previously unsolved roadblocks, which so far have kept dark-field CT from being translated from the optical bench into a rapidly rotating CT gantry, with all its associated challenges like vibrations, continuous rotation, and large field of view. This development enables clinical dark-field CT studies with human patients in the near future.

Whole brain multiparametric mapping in two minutes using a dual-flip-angle stack-of-stars blipped multi-gradient-echo acquisition.

A new MRI technique is presented for three-dimensional fast simultaneous whole brain mapping of myelin water fraction (MWF), T1, proton density (PD), R2*, magnetic susceptibility (QSM), and B1 transmit field (B1+). Phantom and human (N = 9) datasets were acquired using a dual-flip-angle blipped multi-gradient-echo (DFA-mGRE) sequence with a stack-of-stars (SOS) trajectory. Images were reconstructed using a subspace-based algorithm with a locally low-rank constraint. A novel joint-sparsity-constrained multicomponent T2*-T1 spectrum estimation (JMSE) algorithm is proposed to correct for the T1 saturation effect and B1+/B1- inhomogeneities in the quantification of MWF. A tissue-prior-based B1+ estimation algorithm was adapted for B1 correction in the mapping of T1 and PD. In the phantom study, measurements obtained at an acceleration factor (R) of 12 using prospectively under-sampled SOS showed good consistency (R2 > 0.997) with Cartesian reference for R2*/T1app/M0app. In the in vivo study, results of retrospectively under-sampled SOS with R = 6, 12, 18, showed good quality (structure similarity index measure > 0.95) compared with those of fully-sampled SOS. Besides, results of prospectively under-sampled SOS with R = 12 showed good consistency (intraclass correlation coefficient > 0.91) with Cartesian reference for T1/PD/B1+/MWF/QSM/R2*, and good reproducibility (coefficient of variation < 7.0 %) in the test-retest analysis for T1/PD/B1+/MWF/R2*. This study has demonstrated the feasibility of simultaneous whole brain multiparametric mapping with a two-minute scan using the DFA-mGRE SOS sequence, which may overcome a major obstacle for neurological applications of multiparametric MRI.

Ultrahigh-Resolution K-Edge Imaging of Coronary Arteries With Prototype Deep-Silicon Photon-Counting CT: Initial Results in Phantoms.

Background Photon-counting CT (PCCT) represents a recent advancement in CT, offering improved spatial resolution and spectral separability. By using multiple adjustable energy bins, PCCT enables K-edge imaging, allowing mixed contrast agent distinction. Deep-silicon is a new type of photon-counting detector with different characteristics compared with cadmium photon-counting detectors. Purpose To evaluate the performance of a prototype deep-Si PCCT scanner and compare it with that of a state-of-the-art dual-energy energy-integrating detector (EID) scanner in imaging coronary artery plaques enhanced with iodine and K-edge contrast agents. Materials and Methods A series of 10 three-dimensional-printed inserts (diameter, 3.5 mm) was prepared, and materials mimicking soft and calcified plaques were added to simulate stenosed coronary arteries. Inserts filled with an iodine- or gadolinium-based contrast agent (GBCA) were scanned. Virtual monoenergetic images (VMIs) and iodine maps were generated using two- and eight-energy bin data from EID CT and PCCT, respectively. Gadolinium maps were calculated for PCCT. The CT numbers of VMIs and iodine maps were compared. Spatial resolution and blooming artifacts were compared on the 70-keV VMIs in plaque-free and calcified coronary arteries. Results No evidence of a significant difference in the CT number of 70-keV images was found except in inserts containing GBCAs. In the absence of a GBCA, excellent (r > 0.99) agreement for iodine was found. PCCT could quantify the GBCA within 0.2 mg Gd/mL ± 0.8 accuracy of the ground truth, whereas EID CT failed to detect the GBCA. Lumen measurements were more accurate for PCCT than for EID CT, with mean errors of 167 versus 442 µm (P < .001) compared with the 3.5-mm ground truth. Conclusion Deep-Si PCCT demonstrated good accuracy in iodine quantification and could accurately decompose mixtures of two contrast agents. Its improved spatial resolution resulted in sharper images with blooming artifacts reduced by 50% compared with a state-of-the-art dual-energy EID CT scanner. © RSNA, 2024.

Fat Suppression in Distal Extremity 3-T MRI Using Spectral Heterogeneity Adaptive Radiofrequency Pulses.

Background Conventional chemical shift selective (CHESS) fat suppression may fail in distal extremity MRI due to sensitivity to field inhomogeneities. Purpose To develop a patient-specific fat-suppression method for distal extremity 3-T MRI by exploiting the spectral heterogeneity adaptive radiofrequency pulse (SHARP) technique and to compare it to fat suppression with CHESS. Materials and Methods SHARP uses the routinely acquired frequency spectrum at MRI calibration to adapt the frequency range and time-bandwidth product of the fat-suppression pulse. In this prospective study, fat suppression by SHARP was assessed by numerical simulations, phantom experiments, and imaging in 15 asymptomatic participants who underwent ankle, foot, and hand (in superman and hand-by-the-side positions) MRI using SHARP, CHESS, and reference standard (short-tau inversion recovery or Dixon) techniques. Three readers ranked the MRI scans from 1 (best) to 3 (worst) regarding fat-suppression homogeneity. The added value of SHARP was defined as the difference between the proportions of images where SHARP outranked CHESS and where CHESS outranked SHARP. Friedman, Wilcoxon signed rank, and χ2 tests were used to compare in vivo data. Results At numerical simulations, SHARP showed 0% water and 62%-70% fat suppression, whereas CHESS showed 2% water and 57% fat suppression. Phantom data demonstrated lower fat-suppression inhomogeneity indexes with Dixon (1.0%) and SHARP (2.4%) compared with CHESS (10.7%). In 15 participants (mean age, 38.5 years ± 12.8 [SD]; six female participants), mean ranking by readers of fat homogeneity in the reference technique (ankle, foot, hand in superman position, and hand-by-the-side position: 1.02, 1.02, 1.03, and 1.06, respectively) was higher than those with SHARP (1.39, 1.46, 1.50, and 1.66, respectively), which were higher than those with CHESS (1.64, 1.80, 1.61, and 1.80, respectively) (all P < .001). The added value of SHARP was highest for images in the foot (389 of 1158; 33.6%; P < .001 vs other joints), followed by the ankle (247 of 971 [25%]; P < .001 vs both hand positions), and lowest for hand-by-the-side and hand in superman positions (158 of 1223; [13%] and 133 of 1193 [11%], respectively; P = .18). Conclusion SHARP provided more homogeneous fat suppression than CHESS. © RSNA, 2024 Supplemental material is available for this article.

Detectability of Hypoattenuating Liver Lesions with Deep Learning CT Reconstruction: A Phantom and Patient Study.

Background CT deep learning image reconstruction (DLIR) improves image quality by reducing noise compared with adaptive statistical iterative reconstruction-V (ASIR-V). However, objective assessment of low-contrast lesion detectability is lacking. Purpose To investigate low-contrast detectability of hypoattenuating liver lesions on CT scans reconstructed with DLIR compared with CT scans reconstructed with ASIR-V in a patient and a phantom study. Materials and Methods This single-center retrospective study included patients undergoing portal venous phase abdominal CT between February and May 2021 and a low-contrast-resolution phantom scanned with the same protocol. Four reconstructions (ASIR-V at 40% strength [ASIR-V 40] and DLIR at three strengths) were generated. Five radiologists qualitatively assessed the images using the five-point Likert scale for image quality, lesion diagnostic confidence, conspicuity, and small lesion (≤1 cm) visibility. Up to two key lesions per patient, confirmed at histopathologic testing or at prior or follow-up imaging studies, were included. Lesion-to-background contrast-to-noise ratio was calculated. Interreader variability was analyzed. Intergroup qualitative and quantitative metrics were compared between DLIR and ASIR-V 40 using proportional odds logistic regression models. Results Eighty-six liver lesions (mean size, 15 mm ± 9.5 [SD]) in 50 patients (median age, 62 years [IQR, 57-73 years]; 27 [54%] female patients) were included. Differences were not detected for various qualitative low-contrast detectability metrics between ASIR-V 40 and DLIR (P > .05). Quantitatively, medium-strength DLIR and high-strength DLIR yielded higher lesion-to-background contrast-to-noise ratios than ASIR-V 40 (medium-strength DLIR vs ASIR-V 40: odds ratio [OR], 1.96 [95% CI: 1.65, 2.33]; high-strength DLIR vs ASIR-V 40: OR, 5.36 [95% CI: 3.68, 7.82]; P < .001). Low-contrast lesion attenuation was reduced by 2.8-3.6 HU with DLIR. Interreader agreement was moderate to very good for the qualitative metrics. Subgroup analysis based on lesion size of larger than 1 cm and 1 cm or smaller yielded similar results (P > .05). Qualitatively, phantom study results were similar to those in patients (P > .05). Conclusion The detectability of low-contrast liver lesions was similar on CT scans reconstructed with low-, medium-, and high-strength DLIR and ASIR-V 40 in both patient and phantom studies. Lesion-to-background contrast-to-noise ratios were higher for DLIR medium- and high-strength reconstructions compared with ASIR-V 40. © RSNA, 2024 Supplemental material is available for this article.

Precision and Test-Retest Repeatability of Stiffness Measurement with MR Elastography: A Multicenter Phantom Study.

Background MR elastography (MRE) has been shown to have excellent performance for noninvasive liver fibrosis staging. However, there is limited knowledge regarding the precision and test-retest repeatability of stiffness measurement with MRE in the multicenter setting. Purpose To determine the precision and test-retest repeatability of stiffness measurement with MRE across multiple centers using the same phantoms. Materials and Methods In this study, three cylindrical phantoms made of polyvinyl chloride gel mimicking different degrees of liver stiffness in humans (phantoms 1-3: soft, medium, and hard stiffness, respectively) were evaluated. Between January 2021 and January 2022, phantoms were circulated between five different centers and scanned with 10 MRE-equipped clinical 1.5-T and 3-T systems from three major vendors, using two-dimensional (2D) gradient-recalled echo (GRE) imaging and/or 2D spin-echo (SE) echo-planar imaging (EPI). Similar MRE acquisition parameters, hardware, and reconstruction algorithms were used at each center. Mean stiffness was measured by a single observer for each phantom and acquisition on a single section. Stiffness measurement precision and same-session test-retest repeatability were assessed using the coefficient of variation (CV) and the repeatability coefficient (RC), respectively. Results The mean precision represented by the CV was 5.8% (95% CI: 3.8, 7.7) for all phantoms and both sequences combined. For all phantoms, 2D GRE achieved a CV of 4.5% (95% CI: 3.3, 5.7) whereas 2D SE EPI achieved a CV of 7.8% (95% CI: 3.1, 12.6). The mean RC of stiffness measurement was 5.8% (95% CI: 3.7, 7.8) for all phantoms and both sequences combined, 4.9% (95% CI: 2.7, 7.0) for 2D GRE, and 7.0% (95% CI: 2.9, 11.2) for 2D SE EPI (all phantoms). Conclusion MRE had excellent in vitro precision and same-session test-retest repeatability in the multicenter setting when similar imaging protocols, hardware, and reconstruction algorithms were used. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Tang in this issue.

Photon-counting Detector CT for Liver Fat Quantification: Validation across Protocols in Metabolic Dysfunction-associated Steatotic Liver Disease.

Background Traditional energy-integrating detector CT has limited utility in accurately quantifying liver fat due to protocol-induced CT value shifts, but this limitation can be addressed by using photon-counting detector (PCD) CT, which allows for a standardized CT value. Purpose To develop and validate a universal CT to MRI fat conversion formula to enhance fat quantification accuracy across various PCD CT protocols relative to MRI proton density fat fraction (PDFF). Materials and Methods In this prospective study, the feasibility of fat quantification was evaluated in phantoms with various nominal fat fractions. Five hundred asymptomatic participants and 157 participants with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled between September 2023 and March 2024. Participants were randomly assigned to six groups with different CT protocols regarding tube voltage (90, 120, or 140 kVp) and radiation dose (standard or low). Of the participants in the 120-kVp standard-dose asymptomatic group, 51% (53 of 104) were designated as the training cohort, with the rest of the asymptomatic group serving as the validation cohort. A CT to MRI fat quantification formula was derived from the training cohort to estimate the CT-derived fat fraction (CTFF). CTFF agreement with PDFF and its error were evaluated in the asymptomatic validation cohort and subcohorts stratified by tube voltage, radiation dose, and body mass index, and in the MASLD cohort. The factors influencing CTFF error were further evaluated. Results In the phantoms, CTFF showed excellent agreement with nominal fat fraction (intraclass correlation coefficient, 0.98; mean bias, 0.2%). A total of 412 asymptomatic participants and 122 participants with MASLD were included. A CT to MRI fat conversion formula was derived as follows: MRI PDFF (%) = -0.58 · CT (HU) + 43.1. Across all comparisons, CTFF demonstrated excellent agreement with PDFF (mean bias values < 1%). CTFF error was not influenced by tube voltage, radiation dose, body mass index, or PDFF. Agreement between CTFF and PDFF was also found in the MASLD cohort (mean bias, -0.2%). Conclusion Standardized CT value from PCD CT showed a robust and remarkable agreement with MRI PDFF across various protocols and may serve as a precise alternative for liver fat quantification. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wildman-Tobriner in this issue.

Ultrasensitive ultrasound imaging of gene expression with signal unmixing.

Acoustic reporter genes (ARGs) that encode air-filled gas vesicles enable ultrasound-based imaging of gene expression in genetically modified bacteria and mammalian cells, facilitating the study of cellular function in deep tissues. Despite the promise of this technology for biological research and potential clinical applications, the sensitivity with which ARG-expressing cells can be visualized is currently limited. Here we present burst ultrasound reconstructed with signal templates (BURST)-an ARG imaging paradigm that improves the cellular detection limit by more than 1,000-fold compared to conventional methods. BURST takes advantage of the unique temporal signal pattern produced by gas vesicles as they collapse under acoustic pressure above a threshold defined by the ARG. By extracting the unique pattern of this signal from total scattering, BURST boosts the sensitivity of ultrasound to image ARG-expressing cells, as demonstrated in vitro and in vivo in the mouse gastrointestinal tract and liver. Furthermore, in dilute cell suspensions, BURST imaging enables the detection of gene expression in individual bacteria and mammalian cells. The resulting abilities of BURST expand the potential use of ultrasound for non-invasive imaging of cellular functions.

Real-time automatic image-based slice tracking of gadolinium-filled balloon wedge catheter during MR-guided cardiac catheterization: A proof-of-concept study.

PURPOSE: MR-guided cardiac catheterization procedures currently use passive tracking approaches to follow a gadolinium-filled catheter balloon during catheter navigation. This requires frequent manual tracking and repositioning of the imaging slice during navigation. In this study, a novel framework for automatic real-time catheter tracking during MR-guided cardiac catheterization is presented. METHODS: The proposed framework includes two imaging modes (Calibration and Runtime). The sequence starts in Calibration mode, in which the 3D catheter coordinates are determined using a stack of 10-20 contiguous saturated slices combined with real-time image processing. The sequence then automatically switches to Runtime mode, where three contiguous slices (acquired with partial saturation), initially centered on the catheter balloon using the Calibration feedback, are acquired continuously. The 3D catheter balloon coordinates are estimated in real time from each Runtime slice stack using image processing. Each Runtime stack is repositioned to maintain the catheter balloon in the central slice based on the prior Runtime feedback. The sequence switches back to Calibration mode if the catheter is not detected. This framework was evaluated in a heart phantom and 3 patients undergoing MR-guided cardiac catheterization. Catheter detection accuracy and rate of catheter visibility were evaluated. RESULTS: The automatic detection accuracy for the catheter balloon during the Calibration/Runtime mode was 100%/95% in phantom and 100%/97 ± 3% in patients. During Runtime, the catheter was visible in 82% and 98 ± 2% of the real-time measurements in the phantom and patients, respectively. CONCLUSION: The proposed framework enabled real-time continuous automatic tracking of a gadolinium-filled catheter balloon during MR-guided cardiac catheterization.

Deciphering adiabatic rotating frame relaxometry in biological tissues.

PURPOSE: This work aims to unravel the intricacies of adiabatic rotating frame relaxometry in biological tissues. THEORY AND METHODS: The classical formalisms of dipolar relaxation R 1 ρ $$ {R}_{1\rho } $$ and R 2 ρ $$ {R}_{2\rho } $$ were systematically analyzed for water molecules reorienting on "fast" and "slow" timescales. These two timescales are, respectively, responsible for the absence and presence of R 1 ρ $$ {R}_{1\rho } $$ dispersion. A time-averaged R 1 ρ $$ {R}_{1\rho } $$ or R 2 ρ $$ {R}_{2\rho } $$ over an adiabatic pulse duration was recast into a sum of R 1 $$ {R}_1 $$ and R 2 $$ {R}_2 $$ , but with different weightings. These weightings depend on the specific modulations of adiabatic pulse waveforms. In this context, stretched hyperbolic secant ( HSn $$ HSn $$ ) pulses were characterized. Previously published H S 1 $$ HS1 $$ R 1 ρ $$ {R}_{1\rho } $$ , continuous-wave (CW) R 1 ρ $$ {R}_{1\rho } $$ , and R 1 $$ {R}_1 $$ measures from 12 agarose phantoms were used to validate the theoretical predictions. A similar validation was also performed on previously published HSn $$ HSn $$ R 1 ρ $$ {R}_{1\rho } $$ ( n $$ n $$ =1, 4, 8) and HS 1 $$ HS1 $$ R 2 ρ $$ {R}_{2\rho } $$ from bovine cartilage specimens. RESULTS: Longitudinal relaxation weighting decreases for HSn $$ HSn $$ pulses as n $$ n $$ increases. Predicted CW R 1 ρ cal $$ {R}_{1\rho}^{cal} $$ values from agarose phantoms align well with the measured CW R 1 ρ exp $$ {R}_{1\rho}^{exp} $$ values, as indicated by a linear regression function: R 1 ρ cal = 1.04 * R 1 ρ exp - 1.96 $$ {R}_{1\rho}^{cal}={1.04}^{\ast }{R}_{1\rho}^{exp}-1.96 $$ . The predicted adiabatic R 1 ρ $$ {R}_{1\rho } $$ and R 2 ρ $$ {R}_{2\rho } $$ from cartilage specimens are consistent with those previously measured, as quantified by: R 1 ρ , 2 ρ cal = 1.10 * R 1 ρ , 2 ρ exp - 0.41 $$ {R}_{1\rho, 2\rho}^{cal}={1.10}^{\ast }{R}_{1\rho, 2\rho}^{exp}-0.41 $$ . CONCLUSION: This work has theoretically and experimentally demonstrated that adiabatic R 1 ρ $$ {R}_{1\rho } $$ and R 2 ρ $$ {R}_{2\rho } $$ can be recast into a sum of R 1 $$ {R}_1 $$ and R 2 $$ {R}_2 $$ , with varying weightings. Therefore, any suggestions that adiabatic rotating frame relaxometry in biological tissues could provide more information than the standard R 1 $$ {R}_1 $$ and R 2 $$ {R}_2 $$ warrant closer scrutiny.

CMRsim-A python package for cardiovascular MR simulations incorporating complex motion and flow.

PURPOSE: To present an open-source MR simulation framework that facilitates the incorporation of complex motion and flow for studying cardiovascular MR (CMR) acquisition and reconstruction. METHODS: CMRsim is a Python package that allows simulation of CMR images using dynamic digital phantoms with complex motion as input. Two simulation paradigms are available, namely, numerical and analytical solutions to the Bloch equations, using a common motion representation. Competitive simulation speeds are achieved using TensorFlow for GPU acceleration. To demonstrate the capability of the package, one introductory and two advanced CMR simulation experiments are presented. The latter showcase phase-contrast imaging of turbulent flow downstream of a stenotic section and cardiac diffusion tensor imaging on a contracting left ventricle. Additionally, extensive documentation and example resources are provided. RESULTS: The Bloch simulation with turbulent flow using approximately 1.5 million particles and a sequence duration of 710 ms for each of the seven different velocity encodings took a total of 29 min on a NVIDIA Titan RTX GPU. The results show characteristic phase contrast and magnitude modulation present in real data. The analytical simulation of cardiac diffusion tensor imaging with bulk-motion phase sensitivity took approximately 10 s per diffusion-weighted image, including preparation and loading steps. The results exhibit the expected alteration of diffusion metrics due to strain. CONCLUSION: CMRsim is the first simulation framework that allows one to feasibly incorporate complex motion, including turbulent flow, to systematically study advanced CMR acquisition and reconstruction approaches. The open-source package features modularity and transparency, facilitating maintainability and extensibility in support of reproducible research.

The restricted SAR protocol: A method to assess MRI coil prototypes in an unconditionally safe manner.

PURPOSE: Testing an RF coil prototype on subjects involves laborious verifications to ensure its safety. In particular, it requires preliminary electromagnetic simulations and their validations on phantoms to accurately predict the specific absorption rate (SAR). For coil design validation with a simpler safety procedure, the restricted SAR (rS) mode is proposed, enabling representative first experiments in vivo. The goal of the developed approach is to accelerate the transition of a custom coil system from prototype to clinical use. METHODS: The restricted specific absorption rate (SAR) (rS) mode imposes a radical limitation on the transmitted RF power based on a worst-case scenario of local RF power absorption. The limitations used are independent of the SAR spatial distribution, making this approach unconditionally safe. The developed rS protocol contains the sequences required for coil evaluation and satisfies the imposed rS conditions. It provides a quantitative characterization of the coil transmission and reception profiles and a qualitative evaluation of the anatomical images. Protocol validation was performed on commercial and pre-industrial prototype coils on a small cohort of healthy volunteers. RESULTS: The proposed rS protocol enables coil evaluation within an acquisition time compatible with common clinical protocol duration. The total time of all evaluation steps does not exceed 17 min. At the same time, the global SAR remains 100 times less than the International Electrotechnical Commission safety limit for played sequences. CONCLUSION: The rS protocol allows characterizing and comparing coil prototypes on volunteers without extensive electromagnetic calculations and phantom validations in an unconditionally safe way.

Adjustment of rotation and saturation effects (AROSE) for CEST imaging.

PURPOSE: Endogenous CEST signal usually has low specificity due to contaminations from the magnetization transfer contrast (MTC) and other labile protons with overlapping or close Larmor frequencies. We propose to improve CEST signal specificity with adjustment of rotation and saturation effects (AROSE). METHODS: The AROSE approach measures the difference between CEST signals acquired with the same average irradiation power but largely different duty cycles, for example, a continuous wave or a high duty cycle pulse train versus a low duty cycle pulse train with a flip angle φ. Simulation, phantom, and in vivo rodent studies were performed to evaluate the characteristics of the AROSEφ signal. RESULTS: Simulation and experimental results show that AROSE2π is a low-pass filter that can suppress fast exchanging processes (e.g., >3000 s-1 ), whereas AROSEπ is a band-pass filter suppressing both fast and slow exchange (e.g., <30 s-1 ) rates. For other φ angles, the sensitivity and the exchange-rate filtering effect of AROSEφ falls between AROSEπ and AROSE2π . AROSE can also minimize MTC and improve the Larmor frequency selectivity of the CEST signal. The linewidth of the AROSE1.5π spectrum is about 60% to 65% when compared to the CEST spectrum measured by continuous wave. Depending on the needs of an application, the sensitivity, exchange-rate filtering, and Larmor frequency selectivity can be adjusted by varying the flip angle, duty cycle, and average irradiation power. CONCLUSION: Compared to conventional CEST signals, AROSE can minimize MTC and improve exchange rate filtering and Larmor frequency specificity.

Radiation damping at clinical field strength: Characterization and compensation in quantitative measurements.

PURPOSE: In any MR experiment, the bulk magnetization acts on itself, caused by the induced current in the RF receiver circuit that generates an oscillating damping field. This effect, known as "radiation damping" (RD), is usually weak and, therefore, unconsidered in MRI, but can affect quantitative studies performed with dedicated coils that provide a high SNR. The current work examined RD in a setup for investigations of small tissue specimens including a quantitative characterization of the spin-coil system. THEORY AND METHODS: A custom-made Helmholtz coil (radius and spacing 16 mm) was interfaced to a transmit-receive (Tx/Rx) switch with integrated passive feedback for modulation or suppression of RD similar to preamplifier decoupling. Pulse sequences included pulse-width arrays to demonstrate the absence/ presence of RD and difference techniques employing gradient pulses or composite RF pulses to quantify RD effects during free precession and transmission, respectively. Experiments were performed at 3T in small samples of MnCl2 solution. RESULTS: Significant RD effects may impact RF pulse application and evolution periods. Effective damping time constants were comparable to typical T2 * times or echo spacings in multi-echo sequences. Measurements of the phase relation showed that deviations from the commonly assumed 90° angle between the damping field and the transverse magnetization may occur. CONCLUSION: Radiation damping may affect the accuracy of quantitative MR measurements performed with dedicated RF coils. Efficient mitigation can be achieved hardware-based or by appropriate consideration in the pulse sequence.

Beat phenomena of oscillating readouts.

PURPOSE: To demonstrate slowly varying, erroneous magnetic field gradients for oscillating readouts due to the mechanically resonant behavior of gradient systems. METHODS: Projections of a static phantom were acquired using a one-dimensional (1D) EPI sequence with varying EPI frequencies ranging from 1121 to 1580 Hz on clinical 3T systems (30 mT/m, 200 T/m/s). Phase due to static B0 inhomogeneities was eliminated by a complex division of two separate scans with different polarities of the EPI readout. The temporal evolution of phase was evaluated and related to the mechanical resonances of the gradient systems derived from the gradient modulation transfer function. Additionally, the impact of temporally varying mechanical resonance effects on EPI was evaluated using an echo-planar spectroscopic imaging sequence. RESULTS: A beat phenomenon resulting in a slowly varying phase was observed. Its temporal frequency was given by the difference between the EPI frequency and the mechanical resonance frequency of the activated gradient axis. The maximum erroneous, oscillating phase during phase encoding was ±0.5 rad for an EPI frequency of 1281 Hz. Echo-planar spectroscopic imaging images showed the resulting time-dependent stretching/compression of the FOV. CONCLUSION: Oscillating readouts such as those used in EPI can result in low-frequency, erroneous phase contributions, which are explained by the beat phenomenon. Therefore, EPI phase-correction approaches may need to include beat effects for accurate image reconstruction.

Confidence maps for reliable estimation of proton density fat fraction and R 2 * in the liver.

PURPOSE: The objective was to develop a fully automated algorithm that generates confidence maps to identify regions valid for analysis of quantitative proton density fat fraction (PDFF) and R 2 * $$ {R}_2^{\ast } $$ maps of the liver, generated with chemical shift-encoded MRI (CSE-MRI). Confidence maps are urgently needed for automated quality assurance, particularly with the emergence of automated segmentation and analysis algorithms. METHODS: Confidence maps for both PDFF and R 2 * $$ {R}_2^{\ast } $$ maps are generated based on goodness of fit, measured by normalized RMS error between measured complex signals and the CSE-MRI signal model. Based on Cramér-Rao lower bound and Monte-Carlo simulations, normalized RMS error threshold criteria were developed to identify unreliable regions in quantitative maps. Simulation, phantom, and in vivo clinical studies were included. To analyze the clinical data, a board-certified radiologist delineated regions of interest (ROIs) in each of the nine liver segments for PDFF and R 2 * $$ {R}_2^{\ast } $$ analysis in consecutive clinical CSE-MRI data sets. The percent area of ROIs in areas deemed unreliable by confidence maps was calculated to assess the impact of confidence maps on real-world clinical PDFF and R 2 * $$ {R}_2^{\ast } $$ measurements. RESULTS: Simulations and phantom studies demonstrated that the proposed algorithm successfully excluded regions with unreliable PDFF and R 2 * $$ {R}_2^{\ast } $$ measurements. ROI analysis by the radiologist revealed that 2.6% and 15% of the ROIs were placed in unreliable areas of PDFF and R 2 * $$ {R}_2^{\ast } $$ maps, as identified by confidence maps. CONCLUSION: A proposed confidence map algorithm that identifies reliable areas of PDFF and R 2 * $$ {R}_2^{\ast } $$ measurements from CSE-MRI acquisitions was successfully developed. It demonstrated technical and clinical feasibility.

Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters.

PURPOSE: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). METHODS: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood T 1 $$ {\mathrm{T}}_1 $$ relaxation time ( T 1 , B $$ {\mathrm{T}}_{1,B} $$ ) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific T 1 , B $$ {\mathrm{T}}_{1,B} $$ values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. RESULTS: Simulated and phantom experiments showed a strong dependence on AMS and FA ( R 2 $$ {R}^2 $$ >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ( R 2 $$ {R}^2 $$ >0.59) was observed which was reduced when calculating MBF with individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ . For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. CONCLUSION: Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ and a saturation-baseline can reduce these variations in spGRE and improve reproducibility of FAIR-myoASL against acquisition parameters.

Hand-held electron spin resonance scanner for subcutaneous oximetry using OxyChip.

PURPOSE: Electron spin resonance (ESR) is used to measure oxygen partial pressure (pO2) in biological media with many clinical applications. Traditional clinical ESR involves large magnets that encompass the subject of measurement. However, certain applications might benefit from a scanner operating within local static magnetic fields. Our group recently developed such a compact scanner for transcutaneous (surface) pO2 measurements of skin tissue. Here we extend this capability to subsurface (subcutaneous) pO2 measurements and verify it using an artificial tissue emulating (ATE) phantom. METHODS: We introduce a new scanner, tailored for subcutaneous measurements up to 2 mm beneath the skin's surface. This scanner captures pulsed ESR signals from embedded approximate 1-mm oxygen-sensing solid paramagnetic implant, OxyChip. The scanner features a static magnetic field source, producing a uniform region outside its surface, and a compact microwave resonator, for exciting and receiving ESR signals. RESULTS: ESR readings derived from an OxyChip, positioned approximately 1.5 mm from the scanner's surface, embedded in ATE phantom, exhibited a linear relation of 1/T2 versus pO2 for pO2 levels at 0, 7.6, 30, and 160 mmHg, with relative reading accuracy of about 10%. CONCLUSION: The compact ESR scanner can report pO2 data in ATE phantom from an external position relative to the scanner. Implementing this scanner in preclinical and clinical applications for subcutaneous pO2 measurements is a feasible next phase for this development. This innovative design also has the potential to operate in conjunction with artificial skin graft for wound healing, combining therapeutic and pO2 diagnostic features.

Novel pore size-controlled, susceptibility matched, 3D-printed MRI phantoms.

PURPOSE: We report the design concept and fabrication of MRI phantoms, containing blocks of aligned microcapillaires that can be stacked into larger arrays to construct diameter distribution phantoms or fractured, to create a "powder-averaged" emulsion of randomly oriented blocks for vetting or calibrating advanced MRI methods, that is, diffusion tensor imaging, AxCaliber MRI, MAP-MRI, and multiple pulsed field gradient or double diffusion-encoded microstructure imaging methods. The goal was to create a susceptibility-matched microscopically anisotropic but macroscopically isotropic phantom with a ground truth diameter that could be used to vet advanced diffusion methods for diameter determination in fibrous tissues. METHODS: Two-photon polymerization, a novel three-dimensional printing method is used to fabricate blocks of capillaries. Double diffusion encoding methods were employed and analyzed to estimate the expected MRI diameter. RESULTS: Susceptibility-matched microcapillary blocks or modules that can be assembled into large-scale MRI phantoms have been fabricated and measured using advanced diffusion methods, resulting in microscopic anisotropy and random orientation. CONCLUSION: This phantom can vet and calibrate various advanced MRI methods and multiple pulsed field gradient or diffusion-encoded microstructure imaging methods. We demonstrated that two double diffusion encoding methods underestimated the ground truth diameter.