Spatial proteomics in three-dimensional intact specimens.

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of large biological specimens imaged in 3D are lacking. Here, we present DISCO-MS, a technology that combines whole-organ/whole-organism clearing and imaging, deep-learning-based image analysis, robotic tissue extraction, and ultra-high-sensitivity mass spectrometry. DISCO-MS yielded proteome data indistinguishable from uncleared samples in both rodent and human tissues. We used DISCO-MS to investigate microglia activation along axonal tracts after brain injury and characterized early- and late-stage individual amyloid-beta plaques in a mouse model of Alzheimer's disease. DISCO-bot robotic sample extraction enabled us to study the regional heterogeneity of immune cells in intact mouse bodies and aortic plaques in a complete human heart. DISCO-MS enables unbiased proteome analysis of preclinical and clinical tissues after unbiased imaging of entire specimens in 3D, identifying diagnostic and therapeutic opportunities for complex diseases. VIDEO ABSTRACT.

Cellular and Molecular Probing of Intact Human Organs.

Optical tissue transparency permits scalable cellular and molecular investigation of complex tissues in 3D. Adult human organs are particularly challenging to render transparent because of the accumulation of dense and sturdy molecules in decades-aged tissues. To overcome these challenges, we developed SHANEL, a method based on a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to render the intact adult human brain and kidney transparent and perform 3D histology with antibodies and dyes in centimeters-depth. Thereby, we revealed structural details of the intact human eye, human thyroid, human kidney, and transgenic pig pancreas at the cellular resolution. Furthermore, we developed a deep learning pipeline to analyze millions of cells in cleared human brain tissues within hours with standard lab computers. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of large intact mammalian organs.

Deep Learning Reveals Cancer Metastasis and Therapeutic Antibody Targeting in the Entire Body.

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of cancer cells more than 100-fold by applying the vDISCO method to image metastasis in transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantification in 5 different metastatic cancer models including breast, lung, and pancreatic cancer with distinct organotropisms allowed us to systematically analyze features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in entire mice. DeepMACT can thus considerably improve the discovery of effective antibody-based therapeutics at the pre-clinical stage. VIDEO ABSTRACT.

Virtual reality-empowered deep-learning analysis of brain cells.

Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos+ cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin. DELiVR features a comprehensive toolkit for data visualization and can be customized to other cell types of interest, as we did here for microglia somata, using Fiji for dataset-specific training. We applied DELiVR to investigate cancer-related brain activity, unveiling an activation pattern that distinguishes weight-stable cancer from cancers associated with weight loss. Overall, DELiVR is a robust deep-learning tool that does not require advanced coding skills to analyze whole-brain imaging data in health and disease.

Understanding metric-related pitfalls in image analysis validation.

Validation metrics are key for tracking scientific progress and bridging the current chasm between artificial intelligence research and its translation into practice. However, increasing evidence shows that, particularly in image analysis, metrics are often chosen inadequately. Although taking into account the individual strengths, weaknesses and limitations of validation metrics is a critical prerequisite to making educated choices, the relevant knowledge is currently scattered and poorly accessible to individual researchers. Based on a multistage Delphi process conducted by a multidisciplinary expert consortium as well as extensive community feedback, the present work provides a reliable and comprehensive common point of access to information on pitfalls related to validation metrics in image analysis. Although focused on biomedical image analysis, the addressed pitfalls generalize across application domains and are categorized according to a newly created, domain-agnostic taxonomy. The work serves to enhance global comprehension of a key topic in image analysis validation.

Machine learning analysis of whole mouse brain vasculature.

Tissue clearing methods enable the imaging of biological specimens without sectioning. However, reliable and scalable analysis of large imaging datasets in three dimensions remains a challenge. Here we developed a deep learning-based framework to quantify and analyze brain vasculature, named Vessel Segmentation & Analysis Pipeline (VesSAP). Our pipeline uses a convolutional neural network (CNN) with a transfer learning approach for segmentation and achieves human-level accuracy. By using VesSAP, we analyzed the vascular features of whole C57BL/6J, CD1 and BALB/c mouse brains at the micrometer scale after registering them to the Allen mouse brain atlas. We report evidence of secondary intracranial collateral vascularization in CD1 mice and find reduced vascularization of the brainstem in comparison to the cerebrum. Thus, VesSAP enables unbiased and scalable quantifications of the angioarchitecture of cleared mouse brains and yields biological insights into the vascular function of the brain.

Application of machine learning to pretherapeutically estimate dosimetry in men with advanced prostate cancer treated with 177Lu-PSMA I&T therapy.

PURPOSE: Although treatment planning and individualized dose application for emerging prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) are generally recommended, it is still difficult to implement in practice at the moment. In this study, we aimed to prove the concept of pretherapeutic prediction of dosimetry based on imaging and laboratory measurements before the RLT treatment. METHODS: Twenty-three patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA I&T RLT were included retrospectively. They had available pre-therapy 68 Ga-PSMA-HEBD-CC PET/CT and at least 3 planar and 1 SPECT/CT imaging for dosimetry. Overall, 43 cycles of 177Lu-PSMA I&T RLT were applied. Organ-based standard uptake values (SUVs) were obtained from pre-therapy PET/CT scans. Patient dosimetry was calculated for the kidney, liver, spleen, and salivary glands using Hermes Hybrid Dosimetry 4.0 from the planar and SPECT/CT images. Machine learning methods were explored for dose prediction from organ SUVs and laboratory measurements. The uncertainty of these dose predictions was compared with the population-based dosimetry estimates. Mean absolute percentage error (MAPE) was used to assess the prediction uncertainty of estimated dosimetry. RESULTS: An optimal machine learning method achieved a dosimetry prediction MAPE of 15.8 ± 13.2% for the kidney, 29.6% ± 13.7% for the liver, 23.8% ± 13.1% for the salivary glands, and 32.1 ± 31.4% for the spleen. In contrast, the prediction based on literature population mean has significantly larger MAPE (p < 0.01), 25.5 ± 17.3% for the kidney, 139.1% ± 111.5% for the liver, 67.0 ± 58.3% for the salivary glands, and 54.1 ± 215.3% for the spleen. CONCLUSION: The preliminary results confirmed the feasibility of pretherapeutic estimation of treatment dosimetry and its added value to empirical population-based estimation. The exploration of dose prediction may support the implementation of treatment planning for RLT.

Automated detection of the contrast phase in MDCT by an artificial neural network improves the accuracy of opportunistic bone mineral density measurements.

OBJECTIVES: To determine the accuracy of an artificial neural network (ANN) for fully automated detection of the presence and phase of iodinated contrast agent in routine abdominal multidetector computed tomography (MDCT) scans and evaluate the effect of contrast correction for osteoporosis screening. METHODS: This HIPPA-compliant study retrospectively included 579 MDCT scans in 193 patients (62.4 ± 14.6 years, 48 women). Three different ANN models (2D DenseNet with random slice selection, 2D DenseNet with anatomy-guided slice selection, 3D DenseNet) were trained in 462 MDCT scans of 154 patients (threefold cross-validation), who underwent triphasic CT. All ANN models were tested in 117 unseen triphasic scans of 39 patients, as well as in a public MDCT dataset containing 311 patients. In the triphasic test scans, trabecular volumetric bone mineral density (BMD) was calculated using a fully automated pipeline. Root-mean-square errors (RMSE) of BMD measurements with and without correction for contrast application were calculated in comparison to nonenhanced (NE) scans. RESULTS: The 2D DenseNet with anatomy-guided slice selection outperformed the competing models and achieved an F1 score of 0.98 and an accuracy of 98.3% in the test set (public dataset: F1 score 0.93; accuracy 94.2%). Application of contrast agent resulted in significant BMD biases (all p < .001; portal-venous (PV): RMSE 18.7 mg/ml, mean difference 17.5 mg/ml; arterial (AR): RMSE 6.92 mg/ml, mean difference 5.68 mg/ml). After the fully automated correction, this bias was no longer significant (p > .05; PV: RMSE 9.45 mg/ml, mean difference 1.28 mg/ml; AR: RMSE 3.98 mg/ml, mean difference 0.94 mg/ml). CONCLUSION: Automatic detection of the contrast phase in multicenter CT data was achieved with high accuracy, minimizing the contrast-induced error in BMD measurements. KEY POINTS: • A 2D DenseNet with anatomy-guided slice selection achieved an F1 score of 0.98 and an accuracy of 98.3% in the test set. In a public dataset, an F1 score of 0.93 and an accuracy of 94.2% were obtained. • Automated adjustment for contrast injection improved the accuracy of lumbar bone mineral density measurements (RMSE 18.7 mg/ml vs. 9.45 mg/ml respectively, in the portal-venous phase). • An artificial neural network can reliably reveal the presence and phase of iodinated contrast agent in multidetector CT scans ( https://github.com/ferchonavarro/anatomy_guided_contrast_c ). This allows minimizing the contrast-induced error in opportunistic bone mineral density measurements.

Proposed diagnostic volumetric bone mineral density thresholds for osteoporosis and osteopenia at the cervicothoracic spine in correlation to the lumbar spine.

OBJECTIVES: To determine the correlation between cervicothoracic and lumbar volumetric bone mineral density (vBMD) in an average cohort of adults and to identify specific diagnostic thresholds for the cervicothoracic spine on the individual subject level. METHODS: In this HIPPA-compliant study, we retrospectively included 260 patients (59.7 ± 18.3 years, 105 women), who received a contrast-enhanced or non-contrast-enhanced CT scan. vBMD was extracted using an automated pipeline ( https://anduin.bonescreen.de ). The association of vBMD between each vertebra spanning C2-T12 and the averaged values at the lumbar spine (L1-L3) was analyzed before and after semiquantitative assessment of fracture status and degeneration, and respective vertebra-specific cut-off values for osteoporosis were calculated using linear regression. RESULTS: In both women and men, trabecular vBMD decreased with age in the cervical, thoracic, and lumbar regions. vBMD values of cervicothoracic vertebrae showed strong correlations with lumbar vertebrae (L1-L3), with a median Pearson value of r = 0.87 (range: rC2 = 0.76 to rT12 = 0.96). The correlation coefficients were significantly lower (p < 0.0001) without excluding fractured and degenerated vertebrae, median r = 0.82 (range: rC2 = 0.69 to rT12 = 0.93). Respective cut-off values for osteoporosis peaked at C4 (209.2 mg/ml) and decreased to 83.8 mg/ml at T12. CONCLUSION: Our data show a high correlation between clinically used mean L1-L3 values and vBMD values elsewhere in the spine, independent of age. The proposed cut-off values for the cervicothoracic spine therefore may allow the determination of low bone mass even in clinical cases where only parts of the spine are imaged. KEY POINTS: vBMD of all cervicothoracic vertebrae showed strong correlation with lumbar vertebrae (L1-L3), with a median Pearson's correlation coefficient of r = 0.87 (range: rC2 = 0.76 to rT12 = 0.96). The correlation coefficients were significantly lower (p < 0.0001) without excluding fractured and moderate to severely degenerated vertebrae, median r = 0.82 (range: rC2 = 0.69 to rT12 = 0.93). We postulate that trabecular vBMD < 200 mg/ml for the cervical spine and < 100 mg/ml for the thoracic spine are strong indicators of osteoporosis, similar to < 80 mg/ml at the lumbar spine.

Comparing methods of detecting and segmenting unruptured intracranial aneurysms on TOF-MRAS: The ADAM challenge.

Accurate detection and quantification of unruptured intracranial aneurysms (UIAs) is important for rupture risk assessment and to allow an informed treatment decision to be made. Currently, 2D manual measures used to assess UIAs on Time-of-Flight magnetic resonance angiographies (TOF-MRAs) lack 3D information and there is substantial inter-observer variability for both aneurysm detection and assessment of aneurysm size and growth. 3D measures could be helpful to improve aneurysm detection and quantification but are time-consuming and would therefore benefit from a reliable automatic UIA detection and segmentation method. The Aneurysm Detection and segMentation (ADAM) challenge was organised in which methods for automatic UIA detection and segmentation were developed and submitted to be evaluated on a diverse clinical TOF-MRA dataset. A training set (113 cases with a total of 129 UIAs) was released, each case including a TOF-MRA, a structural MR image (T1, T2 or FLAIR), annotation of any present UIA(s) and the centre voxel of the UIA(s). A test set of 141 cases (with 153 UIAs) was used for evaluation. Two tasks were proposed: (1) detection and (2) segmentation of UIAs on TOF-MRAs. Teams developed and submitted containerised methods to be evaluated on the test set. Task 1 was evaluated using metrics of sensitivity and false positive count. Task 2 was evaluated using dice similarity coefficient, modified hausdorff distance (95th percentile) and volumetric similarity. For each task, a ranking was made based on the average of the metrics. In total, eleven teams participated in task 1 and nine of those teams participated in task 2. Task 1 was won by a method specifically designed for the detection task (i.e. not participating in task 2). Based on segmentation metrics, the top two methods for task 2 performed statistically significantly better than all other methods. The detection performance of the top-ranking methods was comparable to visual inspection for larger aneurysms. Segmentation performance of the top ranking method, after selection of true UIAs, was similar to interobserver performance. The ADAM challenge remains open for future submissions and improved submissions, with a live leaderboard to provide benchmarking for method developments at https://adam.isi.uu.nl/.

Automated claustrum segmentation in human brain MRI using deep learning.

In the last two decades, neuroscience has produced intriguing evidence for a central role of the claustrum in mammalian forebrain structure and function. However, relatively few in vivo studies of the claustrum exist in humans. A reason for this may be the delicate and sheet-like structure of the claustrum lying between the insular cortex and the putamen, which makes it not amenable to conventional segmentation methods. Recently, Deep Learning (DL) based approaches have been successfully introduced for automated segmentation of complex, subcortical brain structures. In the following, we present a multi-view DL-based approach to segment the claustrum in T1-weighted MRI scans. We trained and evaluated the proposed method in 181 individuals, using bilateral manual claustrum annotations by an expert neuroradiologist as reference standard. Cross-validation experiments yielded median volumetric similarity, robust Hausdorff distance, and Dice score of 93.3%, 1.41 mm, and 71.8%, respectively, representing equal or superior segmentation performance compared to human intra-rater reliability. The leave-one-scanner-out evaluation showed good transferability of the algorithm to images from unseen scanners at slightly inferior performance. Furthermore, we found that DL-based claustrum segmentation benefits from multi-view information and requires a sample size of around 75 MRI scans in the training set. We conclude that the developed algorithm allows for robust automated claustrum segmentation and thus yields considerable potential for facilitating MRI-based research of the human claustrum. The software and models of our method are made publicly available.

Multi-domain convolutional neural network (MD-CNN) for radial reconstruction of dynamic cardiac MRI.

PURPOSE: Cardiac MR cine imaging allows accurate and reproducible assessment of cardiac function. However, its long scan time not only limits the spatial and temporal resolutions but is challenging in patients with breath-holding difficulty or non-sinus rhythms. To reduce scan time, we propose a multi-domain convolutional neural network (MD-CNN) for fast reconstruction of highly undersampled radial cine images. METHODS: MD-CNN is a complex-valued network that processes MR data in k-space and image domains via k-space interpolation and image-domain subnetworks for residual artifact suppression. MD-CNN exploits spatio-temporal correlations across timeframes and multi-coil redundancies to enable high acceleration. Radial cine data were prospectively collected in 108 subjects (50 ± 17 y, 72 males) using retrospective-gated acquisition with 80%:20% split for training/testing. Images were reconstructed by MD-CNN and k-t Radial Sparse-Sense(kt-RASPS) using an undersampled dataset (14 of 196 acquired views; relative acceleration rate = 14). MD-CNN images were evaluated quantitatively using mean-squared-error (MSE) and structural similarity index (SSIM) relative to reference images, and qualitatively by three independent readers for left ventricular (LV) border sharpness and temporal fidelity using 5-point Likert-scale (1-non-diagnostic, 2-poor, 3-fair, 4-good, and 5-excellent). RESULTS: MD-CNN showed improved MSE and SSIM compared to kt-RASPS (0.11 ± 0.10 vs. 0.61 ± 0.51, and 0.87 ± 0.07 vs. 0.72 ± 0.07, respectively; P < .01). Qualitatively, MD-CCN significantly outperformed kt-RASPS in LV border sharpness (3.87 ± 0.66 vs. 2.71 ± 0.58 at end-diastole, and 3.57 ± 0.6 vs. 2.56 ± 0.6 at end-systole, respectively; P < .01) and temporal fidelity (3.27 ± 0.65 vs. 2.59 ± 0.59; P < .01). CONCLUSION: MD-CNN reduces the scan time of cine imaging by a factor of 23.3 and provides superior image quality compared to kt-RASPS.

Weakly supervised deep learning for determining the prognostic value of 18F-FDG PET/CT in extranodal natural killer/T cell lymphoma, nasal type.

PURPOSE: To develop a weakly supervised deep learning (WSDL) method that could utilize incomplete/missing survival data to predict the prognosis of extranodal natural killer/T cell lymphoma, nasal type (ENKTL) based on pretreatment 18F-FDG PET/CT results. METHODS: One hundred and sixty-seven patients with ENKTL who underwent pretreatment 18F-FDG PET/CT were retrospectively collected. Eighty-four patients were followed up for at least 2 years (training set = 64, test set = 20). A WSDL method was developed to enable the integration of the remaining 83 patients with incomplete/missing follow-up information in the training set. To test generalization, these data were derived from three types of scanners. Prediction similarity index (PSI) was derived from deep learning features of images. Its discriminative ability was calculated and compared with that of a conventional deep learning (CDL) method. Univariate and multivariate analyses helped explore the significance of PSI and clinical features. RESULTS: PSI achieved area under the curve scores of 0.9858 and 0.9946 (training set) and 0.8750 and 0.7344 (test set) in the prediction of progression-free survival (PFS) with the WSDL and CDL methods, respectively. PSI threshold of 1.0 could significantly differentiate the prognosis. In the test set, WSDL and CDL achieved prediction sensitivity, specificity, and accuracy of 87.50% and 62.50%, 83.33% and 83.33%, and 85.00% and 75.00%, respectively. Multivariate analysis confirmed PSI to be an independent significant predictor of PFS in both the methods. CONCLUSION: The WSDL-based framework was more effective for extracting 18F-FDG PET/CT features and predicting the prognosis of ENKTL than the CDL method.

Accelerated 3D whole-brain T1, T2, and proton density mapping: feasibility for clinical glioma MR imaging.

PURPOSE: Advanced MRI-based biomarkers offer comprehensive and quantitative information for the evaluation and characterization of brain tumors. In this study, we report initial clinical experience in routine glioma imaging with a novel, fully 3D multiparametric quantitative transient-state imaging (QTI) method for tissue characterization based on T1 and T2 values. METHODS: To demonstrate the viability of the proposed 3D QTI technique, nine glioma patients (grade II-IV), with a variety of disease states and treatment histories, were included in this study. First, we investigated the feasibility of 3D QTI (6:25 min scan time) for its use in clinical routine imaging, focusing on image reconstruction, parameter estimation, and contrast-weighted image synthesis. Second, for an initial assessment of 3D QTI-based quantitative MR biomarkers, we performed a ROI-based analysis to characterize T1 and T2 components in tumor and peritumoral tissue. RESULTS: The 3D acquisition combined with a compressed sensing reconstruction and neural network-based parameter inference produced parametric maps with high isotropic resolution (1.125 × 1.125 × 1.125 mm3 voxel size) and whole-brain coverage (22.5 × 22.5 × 22.5 cm3 FOV), enabling the synthesis of clinically relevant T1-weighted, T2-weighted, and FLAIR contrasts without any extra scan time. Our study revealed increased T1 and T2 values in tumor and peritumoral regions compared to contralateral white matter, good agreement with healthy volunteer data, and high inter-subject consistency. CONCLUSION: 3D QTI demonstrated comprehensive tissue assessment of tumor substructures captured in T1 and T2 parameters. Aiming for fast acquisition of quantitative MR biomarkers, 3D QTI has potential to improve disease characterization in brain tumor patients under tight clinical time-constraints.

Overdiscrete echo-planar spectroscopic imaging with correlated higher-order phase correction.

PURPOSE: To introduce a robust methodology for fast 1 H MRSI of the brain at 3T with improved SNR and reduced phase-related artifacts. METHOD: An accelerated acquisition scheme using echo-planar spectroscopic imaging (EPSI) was combined with the overdiscrete reconstruction framework. This approach enables the interleaved acquisition of a water reference scan at each phase encoding step, maximizing its correlation with the water-suppressed measurement. Moreover, a generalized high-order phase correction was incorporated into the reconstruction pipeline. The spatial-temporal phase correction term was estimated from the reference scan and interpolated to high resolution using a polynomial basis. The method was implemented at 3T and validated with phantom and in vivo experiments. RESULTS: The methodology showed the elimination of spectral artifacts generated by phase disturbances and achieved mean SNR gains in vivo of 3.18 and 1.19 compared to standard reconstructions with corrections performed at nominal and high resolution, respectively. EPSI scans with interleaved water acquisition showed to be robust to system instabilities and potentially to patient motion. Moreover, phase distortions were effectively corrected in a single step, avoiding additional reference measurements and post-processing steps. CONCLUSION: The overdiscrete reconstruction framework with high-order phase correction allowed to effectively correct for distortions, related to B0 inhomogeneities, B0 drift, eddy currents, and system vibrations. Furthermore, the presented reconstruction method, combined with EPSI acquisitions, demonstrated improved measurement stability, substantial SNR enhancement, better spectral linewidth, and effective artifact removal.

Deep complex convolutional network for fast reconstruction of 3D late gadolinium enhancement cardiac MRI.

Several deep-learning models have been proposed to shorten MRI scan time. Prior deep-learning models that utilize real-valued kernels have limited capability to learn rich representations of complex MRI data. In this work, we utilize a complex-valued convolutional network (ℂNet) for fast reconstruction of highly under-sampled MRI data and evaluate its ability to rapidly reconstruct 3D late gadolinium enhancement (LGE) data. ℂNet preserves the complex nature and optimal combination of real and imaginary components of MRI data throughout the reconstruction process by utilizing complex-valued convolution, novel radial batch normalization, and complex activation function layers in a U-Net architecture. A prospectively under-sampled 3D LGE cardiac MRI dataset of 219 patients (17 003 images) at acceleration rates R = 3 through R = 5 was used to evaluate ℂNet. The dataset was further retrospectively under-sampled to a maximum of R = 8 to simulate higher acceleration rates. We created three reconstructions of the 3D LGE dataset using (1) ℂNet, (2) a compressed-sensing-based low-dimensional-structure self-learning and thresholding algorithm (LOST), and (3) a real-valued U-Net (realNet) with the same number of parameters as ℂNet. LOST-reconstructed data were considered the reference for training and evaluation of all models. The reconstructed images were quantitatively evaluated using mean-squared error (MSE) and the structural similarity index measure (SSIM), and subjectively evaluated by three independent readers. Quantitatively, ℂNet-reconstructed images had significantly improved MSE and SSIM values compared with realNet (MSE, 0.077 versus 0.091; SSIM, 0.876 versus 0.733, respectively; p < 0.01). Subjective quality assessment showed that ℂNet-reconstructed image quality was similar to that of compressed sensing and significantly better than that of realNet. ℂNet reconstruction was also more than 300 times faster than compressed sensing. Retrospective under-sampled images demonstrate the potential of ℂNet at higher acceleration rates. ℂNet enables fast reconstruction of highly accelerated 3D MRI with superior performance to real-valued networks, and achieves faster reconstruction than compressed sensing.

Deep neural network for automatic characterization of lesions on 68Ga-PSMA-11 PET/CT.

PURPOSE: This study proposes an automated prostate cancer (PC) lesion characterization method based on the deep neural network to determine tumor burden on 68Ga-PSMA-11 PET/CT to potentially facilitate the optimization of PSMA-directed radionuclide therapy. METHODS: We collected 68Ga-PSMA-11 PET/CT images from 193 patients with metastatic PC at three medical centers. For proof-of-concept, we focused on the detection of pelvis bone and lymph node lesions. A deep neural network (triple-combining 2.5D U-Net) was developed for the automated characterization of these lesions. The proposed method simultaneously extracts features from axial, coronal, and sagittal planes, which mimics the workflow of physicians and reduces computational and memory requirements. RESULTS: Among all the labeled lesions, the network achieved 99% precision, 99% recall, and an F1 score of 99% on bone lesion detection and 94%, precision 89% recall, and an F1 score of 92% on lymph node lesion detection. The segmentation accuracy is lower than the detection. The performance of the network was correlated with the amount of training data. CONCLUSION: We developed a deep neural network to characterize automatically the PC lesions on 68Ga-PSMA-11 PET/CT. The preliminary test within the pelvic area confirms the potential of deep learning methods. Increasing the amount of training data should further enhance the performance of the proposed method and may ultimately allow whole-body assessments.

Measuring large lipid droplet sizes by probing restricted lipid diffusion effects with diffusion-weighted MRS at 3T.

PURPOSE: The in vivo probing of restricted diffusion effects in large lipid droplets on a clinical MR scanner remains a major challenge due to the need for high b-values and long diffusion times. This work proposes a methodology to probe mean lipid droplet sizes using diffusion-weighted MRS (DW-MRS) at 3T. METHODS: An analytical expression for restricted diffusion was used. Simulations were performed to evaluate the noise performance and the influence of particle size distribution. To validate the method, oil-in-water emulsions were prepared and examined using DW-MRS, laser deflection and light microscopy. The tibia bone marrow was scanned in volunteers to test the method repeatability and characterize microstructural differences at different locations. RESULTS: The simulations showed accurate and precise droplet size estimation when a sufficient SNR is reached with minor dependence on the size distribution. In phantoms, a good correlation between the measured droplet sizes by DW-MRS and by laser deflection (R2 = 0.98; P = 0.01) and microscopy (R2 = 0.99; P < 0.01) measurements was obtained. A mean coefficient of variation of 11.5 % was found for the lipid droplet diameter in vivo. The average diameter was smaller at a proximal (50.1 ± 7.3 µm) compared with a distal tibia location (61.1 ± 6.8 µm) (P < 0.01). CONCLUSION: The presented methods were able to probe restricted diffusion effects in lipid droplets using DW-MRS and to estimate lipid droplet size. The methodology was validated using phantoms and the in vivo feasibility in bone marrow was shown based on a good repeatability and findings in agreement with literature.

S-Leaping: An Adaptive, Accelerated Stochastic Simulation Algorithm, Bridging [Formula: see text]-Leaping and R-Leaping.

We propose the S-leaping algorithm for the acceleration of Gillespie's stochastic simulation algorithm that combines the advantages of the two main accelerated methods; the [Formula: see text]-leaping and R-leaping algorithms. These algorithms are known to be efficient under different conditions; the [Formula: see text]-leaping is efficient for non-stiff systems or systems with partial equilibrium, while the R-leaping performs better in stiff system thanks to an efficient sampling procedure. However, even a small change in a system's set up can critically affect the nature of the simulated system and thus reduce the efficiency of an accelerated algorithm. The proposed algorithm combines the efficient time step selection from the [Formula: see text]-leaping with the effective sampling procedure from the R-leaping algorithm. The S-leaping is shown to maintain its efficiency under different conditions and in the case of large and stiff systems or systems with fast dynamics, the S-leaping outperforms both methods. We demonstrate the performance and the accuracy of the S-leaping in comparison with the [Formula: see text]-leaping and R-leaping on a number of benchmark systems involving biological reaction networks.

Fully convolutional network ensembles for white matter hyperintensities segmentation in MR images.

White matter hyperintensities (WMH) are commonly found in the brains of healthy elderly individuals and have been associated with various neurological and geriatric disorders. In this paper, we present a study using deep fully convolutional network and ensemble models to automatically detect such WMH using fluid attenuation inversion recovery (FLAIR) and T1 magnetic resonance (MR) scans. The algorithm was evaluated and ranked 1st in the WMH Segmentation Challenge at MICCAI 2017. In the evaluation stage, the implementation of the algorithm was submitted to the challenge organizers, who then independently tested it on a hidden set of 110 cases from 5 scanners. Averaged dice score, precision and robust Hausdorff distance obtained on held-out test datasets were 80%, 84% and 6.30 mm respectively. These were the highest achieved in the challenge, suggesting the proposed method is the state-of-the-art. Detailed descriptions and quantitative analysis on key components of the system were provided. Furthermore, a study of cross-scanner evaluation is presented to discuss how the combination of modalities affect the generalization capability of the system. The adaptability of the system to different scanners and protocols is also investigated. A quantitative study is further presented to show the effect of ensemble size and the effectiveness of the ensemble model. Additionally, software and models of our method are made publicly available. The effectiveness and generalization capability of the proposed system show its potential for real-world clinical practice.