Region of interest focused MRI to synthetic CT translation using regression and segmentation multi-task network.

Objective. In MR-only clinical workflow, replacing CT with MR image is of advantage for workflow efficiency and reduces radiation to the patient. An important step required to eliminate CT scan from the workflow is to generate the information provided by CT via an MR image. In this work, we aim to demonstrate a method to generate accurate synthetic CT (sCT) from an MR image to suit the radiation therapy (RT) treatment planning workflow. We show the feasibility of the method and make way for a broader clinical evaluation.Approach. We present a machine learning method for sCT generation from zero-echo-time (ZTE) MRI aimed at structural and quantitative accuracies of the image, with a particular focus on the accurate bone density value prediction. The misestimation of bone density in the radiation path could lead to unintended dose delivery to the target volume and results in suboptimal treatment outcome. We propose a loss function that favors a spatially sparse bone region in the image. We harness the ability of the multi-task network to produce correlated outputs as a framework to enable localization of region of interest (RoI) via segmentation, emphasize regression of values within RoI and still retain the overall accuracy via global regression. The network is optimized by a composite loss function that combines a dedicated loss from each task.Main results. We have included 54 brain patient images in this study and tested the sCT images against reference CT on a subset of 20 cases. A pilot dose evaluation was performed on 9 of the 20 test cases to demonstrate the viability of the generated sCT in RT planning. The average quantitative metrics produced by the proposed method over the test set were-(a) mean absolute error (MAE) of 70 ± 8.6 HU; (b) peak signal-to-noise ratio (PSNR) of 29.4 ± 2.8 dB; structural similarity metric (SSIM) of 0.95 ± 0.02; and (d) Dice coefficient of the body region of 0.984 ± 0.Significance. We demonstrate that the proposed method generates sCT images that resemble visual characteristics of a real CT image and has a quantitative accuracy that suits RT dose planning application. We compare the dose calculation from the proposed sCT and the real CT in a radiation therapy treatment planning setup and show that sCT based planning falls within 0.5% target dose error. The method presented here with an initial dose evaluation makes an encouraging precursor to a broader clinical evaluation of sCT based RT planning on different anatomical regions.

Differentiation between subcentimeter carcinomas and benign lesions using kinetic parameters derived from ultrafast dynamic contrast-enhanced breast MRI.

OBJECTIVES: This study aims to evaluate ultrafast DCE-MRI-derived kinetic parameters that reflect contrast agent inflow effects in differentiating between subcentimeter BI-RADS 4-5 breast carcinomas and benign lesions. METHODS: We retrospectively reviewed consecutive 3-T MRI performed from February to October 2017, during which ultrafast DCE-MRI was performed as part of a hybrid clinical protocol with conventional DCE-MRI. In total, 301 female patients with 369 biopsy-proven breast lesions were included. Ultrafast DCE-MRI was acquired continuously over approximately 60 s (temporal resolution, 2.7-7.1 s/phase) starting simultaneously with the start of contrast injection. Four ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS], contrast enhancement ratio [CER], bolus arrival time [BAT], and initial area under gadolinium contrast agent concentration [IAUGC]) and one conventional DCE-MRI-derived kinetic parameter (signal enhancement ratio [SER]) were calculated for each lesion. Wilcoxon rank sum test or Fisher's exact test was performed to compare kinetic parameters, volume, diameter, age, and BI-RADS morphological descriptors between subcentimeter carcinomas and benign lesions. Univariate/multivariate logistic regression analyses were performed to determine predictive parameters for subcentimeter carcinomas. RESULTS: In total, 125 lesions (26 carcinomas and 99 benign lesions) were identified as BI-RADS 4-5 subcentimeter lesions. Subcentimeter carcinomas demonstrated significantly larger MS and SER and shorter BAT than benign lesions (p = 0.0117, 0.0046, and 0.0102, respectively). MS, BAT, and age were determined as significantly predictive for subcentimeter carcinoma (p = 0.0208, 0.0023, and < 0.0001, respectively). CONCLUSIONS: Ultrafast DCE-MRI-derived kinetic parameters may be useful in differentiating subcentimeter BI-RADS 4 and 5 carcinomas from benign lesions. KEY POINTS: • Ultrafast DCE-MRI can generate kinetic parameters, effectively differentiating breast carcinomas from benign lesions. • Subcentimeter carcinomas demonstrated significantly larger maximum slope and shorter bolus arrival time than benign lesions. • Maximum slope and bolus arrival time contribute to better management of suspicious subcentimeter breast lesions.

Zero TE-based pseudo-CT image conversion in the head and its application in PET/MR attenuation correction and MR-guided radiation therapy planning.

PURPOSE: To describe a method for converting Zero TE (ZTE) MR images into X-ray attenuation information in the form of pseudo-CT images and demonstrate its performance for (1) attenuation correction (AC) in PET/MR and (2) dose planning in MR-guided radiation therapy planning (RTP). METHODS: Proton density-weighted ZTE images were acquired as input for MR-based pseudo-CT conversion, providing (1) efficient capture of short-lived bone signals, (2) flat soft-tissue contrast, and (3) fast and robust 3D MR imaging. After bias correction and normalization, the images were segmented into bone, soft-tissue, and air by means of thresholding and morphological refinements. Fixed Hounsfield replacement values were assigned for air (-1000 HU) and soft-tissue (+42 HU), whereas continuous linear mapping was used for bone. RESULTS: The obtained ZTE-derived pseudo-CT images accurately resembled the true CT images (i.e., Dice coefficient for bone overlap of 0.73 ± 0.08 and mean absolute error of 123 ± 25 HU evaluated over the whole head, including errors from residual registration mismatches in the neck and mouth regions). The linear bone mapping accounted for bone density variations. Averaged across five patients, ZTE-based AC demonstrated a PET error of -0.04 ± 1.68% relative to CT-based AC. Similarly, for RTP assessed in eight patients, the absolute dose difference over the target volume was found to be 0.23 ± 0.42%. CONCLUSION: The described method enables MR to pseudo-CT image conversion for the head in an accurate, robust, and fast manner without relying on anatomical prior knowledge. Potential applications include PET/MR-AC, and MR-guided RTP.

Joint estimation of activity and attenuation for PET using pragmatic MR-based prior: application to clinical TOF PET/MR whole-body data for FDG and non-FDG tracers.

Accurate and robust attenuation correction remains challenging in hybrid PET/MR particularly for torsos because it is difficult to segment bones, lungs and internal air in MR images. Additionally, MR suffers from susceptibility artifacts when a metallic implant is present. Recently, joint estimation (JE) of activity and attenuation based on PET data, also known as maximum likelihood reconstruction of activity and attenuation, has gained considerable interest because of (1) its promise to address the challenges in MR-based attenuation correction (MRAC), and (2) recent advances in time-of-flight (TOF) technology, which is known to be the key to the success of JE. In this paper, we implement a JE algorithm using an MR-based prior and evaluate the algorithm using whole-body PET/MR patient data, for both FDG and non-FDG tracers, acquired from GE SIGNA PET/MR scanners with TOF capability. The weight of the MR-based prior is spatially modulated, based on MR signal strength, to control the balance between MRAC and JE. Large prior weights are used in strong MR signal regions such as soft tissue and fat (i.e. MR tissue classification with a high degree of certainty) and small weights are used in low MR signal regions (i.e. MR tissue classification with a low degree of certainty). The MR-based prior is pragmatic in the sense that it is convex and does not require training or population statistics while exploiting synergies between MRAC and JE. We demonstrate the JE algorithm has the potential to improve the robustness and accuracy of MRAC by recovering the attenuation of metallic implants, internal air and some bones and by better delineating lung boundaries, not only for FDG but also for more specific non-FDG tracers such as 68Ga-DOTATOC and 18F-Fluoride.

Zero-Echo-Time and Dixon Deep Pseudo-CT (ZeDD CT): Direct Generation of Pseudo-CT Images for Pelvic PET/MRI Attenuation Correction Using Deep Convolutional Neural Networks with Multiparametric MRI.

Accurate quantification of uptake on PET images depends on accurate attenuation correction in reconstruction. Current MR-based attenuation correction methods for body PET use a fat and water map derived from a 2-echo Dixon MRI sequence in which bone is neglected. Ultrashort-echo-time or zero-echo-time (ZTE) pulse sequences can capture bone information. We propose the use of patient-specific multiparametric MRI consisting of Dixon MRI and proton-density-weighted ZTE MRI to directly synthesize pseudo-CT images with a deep learning model: we call this method ZTE and Dixon deep pseudo-CT (ZeDD CT). Methods: Twenty-six patients were scanned using an integrated 3-T time-of-flight PET/MRI system. Helical CT images of the patients were acquired separately. A deep convolutional neural network was trained to transform ZTE and Dixon MR images into pseudo-CT images. Ten patients were used for model training, and 16 patients were used for evaluation. Bone and soft-tissue lesions were identified, and the SUVmax was measured. The root-mean-squared error (RMSE) was used to compare the MR-based attenuation correction with the ground-truth CT attenuation correction. Results: In total, 30 bone lesions and 60 soft-tissue lesions were evaluated. The RMSE in PET quantification was reduced by a factor of 4 for bone lesions (10.24% for Dixon PET and 2.68% for ZeDD PET) and by a factor of 1.5 for soft-tissue lesions (6.24% for Dixon PET and 4.07% for ZeDD PET). Conclusion: ZeDD CT produces natural-looking and quantitatively accurate pseudo-CT images and reduces error in pelvic PET/MRI attenuation correction compared with standard methods.

Evaluation of Sinus/Edge-Corrected Zero-Echo-Time-Based Attenuation Correction in Brain PET/MRI.

In brain PET/MRI, the major challenge of zero-echo-time (ZTE)-based attenuation correction (ZTAC) is the misclassification of air/tissue/bone mixtures or their boundaries. Our study aimed to evaluate a sinus/edge-corrected (SEC) ZTAC (ZTACSEC), relative to an uncorrected (UC) ZTAC (ZTACUC) and a CT atlas-based attenuation correction (ATAC). Methods: Whole-body 18F-FDG PET/MRI scans were obtained for 12 patients after PET/CT scans. Only data acquired at a bed station that included the head were used for this study. Using PET data from PET/MRI, we applied ZTACUC, ZTACSEC, ATAC, and reference CT-based attenuation correction (CTAC) to PET attenuation correction. For ZTACUC, the bias-corrected and normalized ZTE was converted to pseudo-CT with air (-1,000 HU for ZTE < 0.2), soft-tissue (42 HU for ZTE > 0.75), and bone (-2,000 × [ZTE - 1] + 42 HU for 0.2 ≤ ZTE ≤ 0.75). Afterward, in the pseudo-CT, sinus/edges were automatically estimated as a binary mask through morphologic processing and edge detection. In the binary mask, the overestimated values were rescaled below 42 HU for ZTACSEC For ATAC, the atlas deformed to MR in-phase was segmented to air, inner air, soft tissue, and continuous bone. For the quantitative evaluation, PET mean uptake values were measured in twenty 1-mL volumes of interest distributed throughout brain tissues. The PET uptake was compared using a paired t test. An error histogram was used to show the distribution of voxel-based PET uptake differences. Results: Compared with CTAC, ZTACSEC achieved the overall PET quantification accuracy (0.2% ± 2.4%, P = 0.23) similar to CTAC, in comparison with ZTACUC (5.6% ± 3.5%, P < 0.01) and ATAC (-0.9% ± 5.0%, P = 0.03). Specifically, a substantial improvement with ZTACSEC (0.6% ± 2.7%, P < 0.01) was found in the cerebellum, in comparison with ZTACUC (8.1% ± 3.5%, P < 0.01) and ATAC (-4.1% ± 4.3%, P < 0.01). The histogram of voxel-based uptake differences demonstrated that ZTACSEC reduced the magnitude and variation of errors substantially, compared with ZTACUC and ATAC. Conclusion: ZTACSEC can provide an accurate PET quantification in brain PET/MRI, comparable to the accuracy achieved by CTAC, particularly in the cerebellum.

Hybrid ZTE/Dixon MR-based attenuation correction for quantitative uptake estimation of pelvic lesions in PET/MRI.

PURPOSE: This study introduces a new hybrid ZTE/Dixon MR-based attenuation correction (MRAC) method including bone density estimation for PET/MRI and quantifies the effects of bone attenuation on metastatic lesion uptake in the pelvis. METHODS: Six patients with pelvic lesions were scanned using fluorodeoxyglucose (18F-FDG) in an integrated time-of-flight (TOF) PET/MRI system. For PET attenuation correction, MR imaging consisted of two-point Dixon and zero echo-time (ZTE) pulse sequences. A continuous-value fat and water pseudoCT was generated from a two-point Dixon MRI. Bone was segmented from the ZTE images and converted to Hounsfield units (HU) using a continuous two-segment piecewise linear model based on ZTE MRI intensity. The HU values were converted to linear attenuation coefficients (LAC) using a bilinear model. The bone voxels of the Dixon-based pseudoCT were replaced by the ZTE-derived bone to produce the hybrid ZTE/Dixon pseudoCT. The three different AC maps (Dixon, hybrid ZTE/Dixon, CTAC) were used to reconstruct PET images using a TOF-ordered subset expectation maximization algorithm with a point-spread function model. Metastatic lesions were separated into two classes, bone lesions and soft tissue lesions, and analyzed. The MRAC methods were compared using a root-mean-squared error (RMSE), where the registered CTAC was taken as ground truth. RESULTS: The RMSE of the maximum standardized uptake values (SUVmax ) is 11.02% and 7.79% for bone (N = 6) and soft tissue lesions (N = 8), respectively, using Dixon MRAC. The RMSE of SUVmax for these lesions is significantly reduced to 3.28% and 3.94% when using the new hybrid ZTE/Dixon MRAC. Additionally, the RMSE for PET SUVs across the entire pelvis and all patients are 8.76% and 4.18%, for the Dixon and hybrid ZTE/Dixon MRAC methods, respectively. CONCLUSION: A hybrid ZTE/Dixon MRAC method was developed and applied to pelvic regions in an integrated TOF PET/MRI, demonstrating improved MRAC. This new method included bone density estimation, through which PET quantification is improved.

Bolus arrival time and its effect on tissue characterization with dynamic contrast-enhanced magnetic resonance imaging.

Matching the bolus arrival time (BAT) of the arterial input function (AIF) and tissue residue function (TRF) is necessary for accurate pharmacokinetic (PK) modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We investigated the sensitivity of volume transfer constant ([Formula: see text]) and extravascular extracellular volume fraction ([Formula: see text]) to BAT and compared the results of four automatic BAT measurement methods in characterization of prostate and breast cancers. Variation in delay between AIF and TRF resulted in a monotonous change trend of [Formula: see text] and [Formula: see text] values. The results of automatic BAT estimators for clinical data were all comparable except for one BAT estimation method. Our results indicate that inaccuracies in BAT measurement can lead to variability among DCE-MRI PK model parameters, diminish the quality of model fit, and produce fewer valid voxels in a region of interest. Although the selection of the BAT method did not affect the direction of change in the treatment assessment cohort, we suggest that BAT measurement methods must be used consistently in the course of longitudinal studies to control measurement variability.

Zero TE MR bone imaging in the head.

PURPOSE: To investigate proton density (PD)-weighted zero TE (ZT) imaging for morphological depiction and segmentation of cranial bone structures. METHODS: A rotating ultra-fast imaging sequence (RUFIS) type ZT pulse sequence was developed and optimized for 1) efficient capture of short T2 bone signals and 2) flat PD response for soft-tissues. An inverse logarithmic image scaling (i.e., -log(image)) was used to highlight bone and differentiate it from surrounding soft-tissue and air. Furthermore, a histogram-based bias-correction method was developed for subsequent threshold-based air, soft-tissue, and bone segmentation. RESULTS: PD-weighted ZT imaging in combination with an inverse logarithmic scaling was found to provide excellent depiction of cranial bone structures. In combination with bias correction, also excellent segmentation results were achieved. A two-dimensional histogram analysis demonstrates a strong, approximately linear correlation between inverse log-scaled ZT and low-dose CT for Hounsfield units (HU) between -300 HU and 1,500 HU (corresponding to soft-tissue and bone). CONCLUSIONS: PD-weighted ZT imaging provides robust and efficient depiction of bone structures in the head, with an excellent contrast between air, soft-tissue, and bone. Besides structural bone imaging, the presented method is expected to be of relevance for attenuation correction in positron emission tomography (PET)/MR and MR-based radiation therapy planning.

Clinical evaluation of zero-echo-time MR imaging for the segmentation of the skull.

UNLABELLED: MR-based attenuation correction is instrumental for integrated PET/MR imaging. It is generally achieved by segmenting MR images into a set of tissue classes with known attenuation properties (e.g., air, lung, bone, fat, soft tissue). Bone identification with MR imaging is, however, quite challenging, because of the low proton density and fast decay time of bone tissue. The clinical evaluation of a novel, recently published method for zero-echo-time (ZTE)-based MR bone depiction and segmentation in the head is presented here. METHODS: A new paradigm for MR imaging bone segmentation, based on proton density-weighted ZTE imaging, was disclosed earlier in 2014. In this study, we reviewed the bone maps obtained with this method on 15 clinical datasets acquired with a PET/CT/MR trimodality setup. The CT scans acquired for PET attenuation-correction purposes were used as reference for the evaluation. Quantitative measurements based on the Jaccard distance between ZTE and CT bone masks and qualitative scoring of anatomic accuracy by an experienced radiologist and nuclear medicine physician were performed. RESULTS: The average Jaccard distance between ZTE and CT bone masks evaluated over the entire head was 52% ± 6% (range, 38%-63%). When only the cranium was considered, the distance was 39% ± 4% (range, 32%-49%). These results surpass previously reported attempts with dual-echo ultrashort echo time, for which the Jaccard distance was in the 47%-79% range (parietal and nasal regions, respectively). Anatomically, the calvaria is consistently well segmented, with frequent but isolated voxel misclassifications. Air cavity walls and bone/fluid interfaces with high anatomic detail, such as the inner ear, remain a challenge. CONCLUSION: This is the first, to our knowledge, clinical evaluation of skull bone identification based on a ZTE sequence. The results suggest that proton density-weighted ZTE imaging is an efficient means of obtaining high-resolution maps of bone tissue with sufficient anatomic accuracy for, for example, PET attenuation correction.

Real-time liver motion compensation for MRgFUS.

MR-guided focused ultrasound (MRgFUS) is a non-invasive method by which tissue is ablated using ultrasound energy focused on a point. The procedure has proven effective for stationary targets (e.g. uterine fibroids) but has not yet been used for liver lesion treatment due to organ motion. We describe a method to compensate for organ motion to enable continuous application of ultrasound energy in the presence of target movement in the liver. The method involves tracking several salient features (typically blood vessels) in the vicinity of the target location. The location of the target point(s) themselves are updated using a thin plate spline (TPS) interpolation scheme. We demonstrate sub-pixel tracking accuracy on synthetic sequences and additionally show results on MRI sequences acquired on human subjects. Per-feature tracking times were measured to be 5.7ms with a standard deviation of 1.6ms, sufficient for real-time use.

q-Space analysis of lung morphometry in vivo with hyperpolarized 3He spectroscopy.

PURPOSE: To examine the utility of a (3)He spectroscopic q-space technique for detecting changes in lung morphometry in vivo. MATERIALS AND METHODS: A diffusion-weighted spectroscopy sequence was used to collect global diffusion data from healthy adults (N = 11), healthy children (N = 5), and chronic obstructive pulmonary disease (COPD) patients (N = 2) using 40 cc of hyperpolarized (3)He gas within a two second breathhold. Displacement probability profiles (DPP) were obtained by Fourier transformation of diffusion data with respect to q. A bi-Gaussian model was used to decompose the DPPs into narrow and broad components, characterized by root-mean-square displacements X(rms1) and X(rms2), respectively. RESULTS: In healthy adults, the narrow component (X(rms,1)) of the DPP had a mean displacement of 188 +/- 10 microm, slightly less than the reported average size of the alveoli. The broad component (X(rms,2)) had a mean value of 474 +/- 44 microm, comparable to the diameter of the respiratory bronchioles in the acinus. In children, both X(rms1) (167 +/- 4 microm) and X(rms2) (382 +/- 22 microm) compared to healthy adults (P < 0.01). In COPD patients, the mean displacements were elevated (X(rms1): 265 +/- 71 microm; X(rms2): 530 +/- 109 microm) compared to healthy adults. Excellent correlation was found between rms displacements and age (age vs. X(rms,1): r = 0.78, P < 0.001; age vs. X(rms,2): r = 0.90, P < 0.001). CONCLUSION: The q-space parameters agreed remarkably well with published alveolar morphometry data. The results suggest that the technique may be sensitive to disease, as evident from the elevated mean displacements in COPD patients compared to healthy volunteers. Detailed lung microstructural information can be obtained using a very low volume of inhaled (3)He.

A phase rotation scheme for achieving very short echo times with localized stimulated echo spectroscopy.

In a single-voxel stimulated echo localization sequence in magnetic resonance spectroscopy, magnetic field gradients are inserted within the echo time (TE) to filter signals generated through coherence pathways other than that leading to the stimulated echo. There is a significant penalty for these gradients as they increase the minimum TE, thereby leading to significant signal loss from spin-spin relaxation and phase distortions in coupled spin systems. Here, an RF phase rotation technique is described for a stimulated echo localization sequence that allows removal of the gradients in the TE intervals and, subsequently, reduction of the minimum TE to only 6 ms. Experiments carried out on six healthy volunteers on a 1.5-T whole-body MR system show a significant signal increase in the metabolite concentrations when measured with a 6-ms TE (N-acetyl-aspartate, 12%, P=.002; creatine, 15%, P=.04; and glutamate+glutamine, 92%, P=.02) compared to concentrations measured with data collected at TEs of 15 and 20 ms.

Increasing the speed of relaxometry-based compartmental analysis experiments in STEAM spectroscopy.

In this work we present a method for improving the speed of spin-spin relaxation time (T2) measurements for compartmental analysis in stimulated echo localized magnetic resonance spectroscopy without reducing the sampling density. The technique uses a progressive repetition time (TR) to compensate for echo time (TE) dependent variations in saturation effects that would otherwise modulate the received signal at short TRs. The method was validated in T2 studies on 10 young healthy subjects in spectroscopic voxels localized along either the right or left Sylvian fissure (2 x 2 x 1.5 cm3, 10 ms mixing time (TM), 2048 data points, 819.2 ms acquisition time). The TR was automatically adjusted so that TR-TM-TE/2 was kept constant as the TE was incremented. Compared to long TR T2 experiments, the progressive TR technique consistently replicated the T2 relaxation times and reference signals of the tissue water compartment while reducing the data acquisition time by more than 50%. The percent error was on average less than 2% for estimates of T2 and S(0) for the tissue water, an indication that the progressive TR technique is a useful method for determining the tissue water signal for internal referencing.