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Richard Laforest

Publications and source records attributed to Richard Laforest.

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Progress in SPECT and PET Reconstruction for Theranostics: From Diagnosis to Therapy

The theranostic paradigm enables personalization of treatment by selecting patients with a diagnostic radiopharmaceutical and monitoring therapy using a matched therapeutic isotope. This strategy relies on accurate image reconstruction of both pretherapy and post-therapy images for patient selection and monitoring treatment. However, traditional reconstruction methods are hindered by challenges such as crosstalk in multi-isotope imaging and extremely low-count measurements data when imaging of alpha-emitting isotopes. Additionally, to fully realize the benefits of new imaging systems being developed for theranostic applications, advanced reconstruction techniques are needed. This review highlights recent progress and discusses critical challenges and unmet needs in theranostic image reconstruction.

physics.med-ph

Objective Task-based Evaluation of Quantitative Medical Imaging Methods: Emerging Frameworks and Future Directions

Quantitative imaging (QI) is demonstrating strong promise across multiple clinical applications. For clinical translation of QI methods, objective evaluation on clinically relevant tasks is essential. To address this need, multiple evaluation strategies are being developed. In this paper, based on previous literature, we outline four emerging frameworks to perform evaluation studies of QI methods. We first discuss the use of virtual imaging trials (VITs) to evaluate QI methods. Next, we outline a no-gold-standard evaluation framework to clinically evaluate QI methods without ground truth. Third, a framework to evaluate QI methods for joint detection and quantification tasks is outlined. Finally, we outline a framework to evaluate QI methods that output multi-dimensional parameters, such as radiomic features. We review these frameworks, discussing their utilities and limitations. Further, we examine future research areas in evaluation of QI methods. Given the recent advancements in PET, including long axial field-of-view scanners and the development of artificial-intelligence algorithms, we present these frameworks in the context of PET.

physics.med-ph

Development and in silico imaging trial evaluation of a deep-learning-based transmission-less attenuation compensation method for DaT SPECT

Quantitative measures of dopamine transporter (DaT) uptake in caudate, putamen, and globus pallidus derived from DaT-single-photon emission computed tomography (SPECT) images are being investigated as biomarkers to diagnose, assess disease status, and track the progression of Parkinsonism. Reliable quantification from DaT-SPECT images requires performing attenuation compensation (AC), typically with a separate X-ray CT scan. Such CT-based AC (CTAC) has multiple challenges, a key one being the non-availability of X-ray CT component on many clinical SPECT systems. Even when a CT is available, the additional CT scan leads to increased radiation dose, costs, and complexity, potential quantification errors due to SPECT-CT misalignment, and higher training and regulatory requirements. To overcome the challenges with the requirement of a CT scan for AC in DaT SPECT, we propose a deep learning (DL)-based transmission-less AC method for DaT-SPECT (DaT-CTLESS). An in silico imaging trial, titled ISIT-DaT, was designed to evaluate the performance of DaT-CTLESS on the regional uptake quantification task. We observed that DaT-CTLESS yielded a significantly higher correlation with CTAC than that between UAC and CTAC on the regional DaT uptake quantification task. Further, DaT-CLTESS had an excellent agreement with CTAC on this task, significantly outperformed UAC in distinguishing patients with normal versus reduced putamen SBR, yielded good generalizability across two scanners, was generally insensitive to intra-regional uptake heterogeneity, demonstrated good repeatability, exhibited robust performance even as the size of the training data was reduced, and generally outperformed the other considered DL methods on the task of quantifying regional uptake across different training dataset sizes. These results provide a strong motivation for further clinical evaluation of DaT-CTLESS.

physics.med-ph

CTLESS: A scatter-window projection and deep learning-based transmission-less attenuation compensation method for myocardial perfusion SPECT

Attenuation compensation (AC), while being beneficial for visual-interpretation tasks in myocardial perfusion imaging (MPI) by SPECT, typically requires the availability of a separate X-ray CT component, leading to additional radiation dose, higher costs, and potentially inaccurate diagnosis due to SPECT/CT misalignment. To address these issues, we developed a method for cardiac SPECT AC using deep learning and emission scatter-window photons without a separate transmission scan (CTLESS). In this method, an estimated attenuation map reconstructed from scatter-energy window projections is segmented into different regions using a multi-channel input multi-decoder network trained on CT scans. Pre-defined attenuation coefficients are assigned to these regions, yielding the attenuation map used for AC. We objectively evaluated this method in a retrospective study with anonymized clinical SPECT/CT stress MPI images on the clinical task of detecting defects with an anthropomorphic model observer. CTLESS yielded statistically non-inferior performance compared to a CT-based AC (CTAC) method and significantly outperformed a non-AC (NAC) method on this clinical task. Similar results were observed in stratified analyses with different sexes, defect extents and severities. The method was observed to generalize across two SPECT scanners, each with a different camera. In addition, CTLESS yielded similar performance as CTAC and outperformed NAC method on the metrics of root mean squared error and structural similarity index measure. Moreover, as we reduced the training dataset size, CTLESS yielded relatively stable AUC values and generally outperformed another DL-based AC method that directly estimated the attenuation coefficient within each voxel. These results demonstrate the capability of the CTLESS method for transmission-less AC in SPECT and motivate further clinical evaluation.

physics.med-ph

Joint regional uptake quantification of Thorium-227 and Radium-223 using a multiple-energy-window projection-domain quantitative SPECT method

Thorium-227-based alpha-particle radiopharmaceutical therapies (α-RPTs) are being investigated in several clinical and pre-clinical studies. After administration, Thorium-227 decays to Radium-223, another alpha-particle-emitting isotope, which redistributes within the patient. Reliable dose quantification of both Thorium-227 and Radium-223 is clinically important, and SPECT may perform this quantification as these isotopes also emit X- and gamma-ray photons. However, reliable quantification is challenged by the orders-of-magnitude lower activity compared to conventional SPECT, resulting in a very low number of detected counts, the presence of multiple photopeaks, substantial overlap in the emission spectra of these isotopes, and the image-degrading effects in SPECT. To address these issues, we propose a multiple-energy-window projection-domain quantification (MEW-PDQ) method that jointly estimates the regional activity uptake of both Thorium-227 and Radium-223 directly using the SPECT projection from multiple energy windows. We evaluated the method with realistic simulation studies using anthropomorphic digital phantoms, in the context of imaging patients with bone metastases of prostate cancer and treated with Thorium-227-based α-RPTs. The proposed method yielded reliable (accurate and precise) regional uptake estimates of both isotopes and outperformed state-of-the-art methods across different lesion sizes and contrasts, in a virtual imaging trial, as well as with moderate levels of intra-regional heterogeneous uptake and with moderate inaccuracies in the definitions of the support of various regions. Additionally, we demonstrated the effectiveness of using multiple energy windows and the variance of the estimated uptake using the proposed method approached the Cramér-Rao-lower-bound-defined theoretical limit.

physics.med-ph

DEMIST: A deep-learning-based task-specific denoising approach for myocardial perfusion SPECT

There is an important need for methods to process myocardial perfusion imaging (MPI) SPECT images acquired at lower radiation dose and/or acquisition time such that the processed images improve observer performance on the clinical task of detecting perfusion defects. To address this need, we build upon concepts from model-observer theory and our understanding of the human visual system to propose a Detection task-specific deep-learning-based approach for denoising MPI SPECT images (DEMIST). The approach, while performing denoising, is designed to preserve features that influence observer performance on detection tasks. We objectively evaluated DEMIST on the task of detecting perfusion defects using a retrospective study with anonymized clinical data in patients who underwent MPI studies across two scanners (N = 338). The evaluation was performed at low-dose levels of 6.25%, 12.5% and 25% and using an anthropomorphic channelized Hotelling observer. Performance was quantified using area under the receiver operating characteristics curve (AUC). Images denoised with DEMIST yielded significantly higher AUC compared to corresponding low-dose images and images denoised with a commonly used task-agnostic DL-based denoising method. Similar results were observed with stratified analysis based on patient sex and defect type. Additionally, DEMIST improved visual fidelity of the low-dose images as quantified using root mean squared error and structural similarity index metric. A mathematical analysis revealed that DEMIST preserved features that assist in detection tasks while improving the noise properties, resulting in improved observer performance. The results provide strong evidence for further clinical evaluation of DEMIST to denoise low-count images in MPI SPECT.

physics.med-ph

A list-mode multi-energy window low-count SPECT reconstruction method for isotopes with multiple emission peaks

SPECT provides a mechanism to perform absorbed-dose quantification tasks for $α$-particle radiopharmaceutical therapies ($α$-RPTs). However, quantitative SPECT for $α$-RPT is challenging due to the low number of detected counts, the complex emission spectrum, and other image-degrading artifacts. Towards addressing these challenges, we propose a low-count quantitative SPECT reconstruction method for isotopes with multiple emission peaks. Given the low-count setting, it is important that the reconstruction method extract the maximal possible information from each detected photon. Processing data over multiple energy windows and in list-mode (LM) format provide mechanisms to achieve that objective. Towards this goal, we propose a list-mode multi-energy window (LM-MEW) OSEM-based SPECT reconstruction method that uses data from multiple energy windows in LM format, and includes the energy attribute of each detected photon. For computational efficiency, we developed a multi-GPU-based implementation of this method. The method was evaluated using 2-D SPECT simulation studies in a single-scatter setting conducted in the context of imaging [$^{223}$Ra]RaCl${_2}$. The proposed method yielded improved performance on the task of estimating activity uptake within known regions of interest in comparison to approaches that use a single energy window or use binned data. The improved performance was observed in terms of both accuracy and precision and for different sizes of the region of interest. Results of our studies show that the use of multiple energy windows and processing data in LM format with the proposed LM-MEW method led to improved quantification performance in low-count SPECT of isotopes with multiple emission peaks. These results motivate further development and validation of the LM-MEW method for such imaging applications, including for $α$-RPT SPECT.

physics.med-ph

Need for Objective Task-based Evaluation of Deep Learning-Based Denoising Methods: A Study in the Context of Myocardial Perfusion SPECT

Artificial intelligence-based methods have generated substantial interest in nuclear medicine. An area of significant interest has been using deep-learning (DL)-based approaches for denoising images acquired with lower doses, shorter acquisition times, or both. Objective evaluation of these approaches is essential for clinical application. DL-based approaches for denoising nuclear-medicine images have typically been evaluated using fidelity-based figures of merit (FoMs) such as RMSE and SSIM. However, these images are acquired for clinical tasks and thus should be evaluated based on their performance in these tasks. Our objectives were to (1) investigate whether evaluation with these FoMs is consistent with objective clinical-task-based evaluation; (2) provide a theoretical analysis for determining the impact of denoising on signal-detection tasks; (3) demonstrate the utility of virtual clinical trials (VCTs) to evaluate DL-based methods. A VCT to evaluate a DL-based method for denoising myocardial perfusion SPECT (MPS) images was conducted. The impact of DL-based denoising was evaluated using fidelity-based FoMs and AUC, which quantified performance on detecting perfusion defects in MPS images as obtained using a model observer with anthropomorphic channels. Based on fidelity-based FoMs, denoising using the considered DL-based method led to significantly superior performance. However, based on ROC analysis, denoising did not improve, and in fact, often degraded detection-task performance. The results motivate the need for objective task-based evaluation of DL-based denoising approaches. Further, this study shows how VCTs provide a mechanism to conduct such evaluations using VCTs. Finally, our theoretical treatment reveals insights into the reasons for the limited performance of the denoising approach.

eess.IV

Synthetic PET via Domain Translation of 3D MRI

Historically, patient datasets have been used to develop and validate various reconstruction algorithms for PET/MRI and PET/CT. To enable such algorithm development, without the need for acquiring hundreds of patient exams, in this paper we demonstrate a deep learning technique to generate synthetic but realistic whole-body PET sinograms from abundantly-available whole-body MRI. Specifically, we use a dataset of 56 $^{18}$F-FDG-PET/MRI exams to train a 3D residual UNet to predict physiologic PET uptake from whole-body T1-weighted MRI. In training we implemented a balanced loss function to generate realistic uptake across a large dynamic range and computed losses along tomographic lines of response to mimic the PET acquisition. The predicted PET images are forward projected to produce synthetic PET time-of-flight (ToF) sinograms that can be used with vendor-provided PET reconstruction algorithms, including using CT-based attenuation correction (CTAC) and MR-based attenuation correction (MRAC). The resulting synthetic data recapitulates physiologic $^{18}$F-FDG uptake, e.g. high uptake localized to the brain and bladder, as well as uptake in liver, kidneys, heart and muscle. To simulate abnormalities with high uptake, we also insert synthetic lesions. We demonstrate that this synthetic PET data can be used interchangeably with real PET data for the PET quantification task of comparing CT and MR-based attenuation correction methods, achieving $\leq 7.6\%$ error in mean-SUV compared to using real data. These results together show that the proposed synthetic PET data pipeline can be reasonably used for development, evaluation, and validation of PET/MRI reconstruction methods.

physics.med-ph

A tissue-fraction estimation-based segmentation method for quantitative dopamine transporter SPECT

Quantitative measures of dopamine transporter (DaT) uptake in caudate, putamen, and globus pallidus (GP) have potential as biomarkers for measuring the severity of Parkinson disease. Reliable quantification of this uptake requires accurate segmentation of the considered regions. However, segmentation of these regions from DaT-SPECT images is challenging, a major reason being partial-volume effects (PVEs), which arise from the limited system resolution and reconstruction of images over finite-sized voxel grids. The latter leads to tissue-fraction effects (TFEs). Thus, there is an important need for methods that can account for the PVEs, including the TFEs, and accurately segment DaT-SPECT images. The purpose of this study is to design and objectively evaluate a fully automated tissue-fraction estimation-based segmentation method that segments the caudate, putamen, and GP from DaT-SPECT images. The proposed method estimates the posterior mean of the fractional volumes occupied by the caudate, putamen, and GP within each voxel of a 3-D DaT-SPECT image. The estimate is obtained by minimizing a cost function based on the binary cross-entropy loss between the true and estimated fractional volumes over a population of SPECT images. Evaluations using clinically guided highly realistic simulation studies show that the proposed method accurately segmented the caudate, putamen, and GP with high mean Dice similarity coefficients ~ 0.80 and significantly outperformed (p < 0.01) all other considered segmentation methods. Further, objective evaluation of the proposed method on the task of quantifying regional uptake shows that the method yielded reliable quantification with low ensemble normalized root mean square error (NRMSE) < 20% for all the considered regions. The results motivate further evaluation of the method with physical-phantom and patient studies.

physics.med-ph

A Bayesian approach to tissue-fraction estimation for oncological PET segmentation

Tumor segmentation in oncological PET is challenging, a major reason being the partial-volume effects that arise due to low system resolution and finite voxel size. The latter results in tissue-fraction effects, i.e. voxels contain a mixture of tissue classes. Conventional segmentation methods are typically designed to assign each voxel in the image as belonging to a certain tissue class. Thus, these methods are inherently limited in modeling tissue-fraction effects. To address the challenge of accounting for partial-volume effects, and in particular, tissue-fraction effects, we propose a Bayesian approach to tissue-fraction estimation for oncological PET segmentation. Specifically, this Bayesian approach estimates the posterior mean of fractional volume that the tumor occupies within each voxel of the image. The proposed method, implemented using a deep-learning-based technique, was first evaluated using clinically realistic 2-D simulation studies with known ground truth, in the context of segmenting the primary tumor in PET images of patients with lung cancer. The evaluation studies demonstrated that the method accurately estimated the tumor-fraction areas and significantly outperformed widely used conventional PET segmentation methods, including a U-net-based method, on the task of segmenting the tumor. In addition, the proposed method was relatively insensitive to partial-volume effects and yielded reliable tumor segmentation for different clinical-scanner configurations. The method was then evaluated using clinical images of patients with stage IIB/III non-small cell lung cancer from ACRIN 6668/RTOG 0235 multi-center clinical trial. Here, the results showed that the proposed method significantly outperformed all other considered methods and yielded accurate tumor segmentation on patient images with Dice similarity coefficient (DSC) of 0.82 (95 % CI: [0.78, 0.86]).

physics.med-ph

A projection-domain low-count quantitative SPECT method for alpha-particle emitting radiopharmaceutical therapy

Single-photon emission computed tomography (SPECT) provides a mechanism to estimate regional isotope uptake in lesions and at-risk organs after administration of α-particle-emitting radiopharmaceutical therapies (α-RPTs). However, this estimation task is challenging due to the complex emission spectra, the very low number of detected counts, the impact of stray-radiation-related noise at these low counts, and the multiple image-degrading processes in SPECT. The conventional reconstruction-based quantification methods are observed to be erroneous for α-RPT SPECT. To address these challenges, we developed a low-count quantitative SPECT (LC-QSPECT) method that directly estimates the regional activity uptake from the projection data, compensates for stray-radiation-related noise, and for the radioisotope and SPECT physics. The method was validated in the context of three-dimensional SPECT with 223 Ra. Validation was performed using both realistic simulation studies, including a virtual clinical trial, and synthetic and anthropomorphic physical-phantom studies. Across all studies, the LC-QSPECT method yielded reliable regional-uptake estimates and outperformed the conventional ordered subset expectation maximization (OSEM)-based reconstruction and geometric transfer matrix (GTM)-based post-reconstruction partial-volume compensation methods. Further, the method yielded reliable uptake across different lesion sizes, contrasts, and different levels of intra-lesion heterogeneity. Additionally, the variance of the estimated uptake approached the Cramé-Rao bound-defined theoretical limit.

physics.med-ph

Observer study-based evaluation of a stochastic and physics-based method to generate oncological PET images

Objective evaluation of new and improved methods for PET imaging requires access to images with ground truth, as can be obtained through simulation studies. However, for these studies to be clinically relevant, it is important that the simulated images are clinically realistic. In this study, we develop a stochastic and physics-based method to generate realistic oncological two-dimensional (2-D) PET images, where the ground-truth tumor properties are known. The developed method extends upon a previously proposed approach. The approach captures the observed variabilities in tumor properties from actual patient population. Further, we extend that approach to model intra-tumor heterogeneity using a lumpy object model. To quantitatively evaluate the clinical realism of the simulated images, we conducted a human-observer study. This was a two-alternative forced-choice (2AFC) study with trained readers (five PET physicians and one PET physicist). Our results showed that the readers had an average of ~ 50% accuracy in the 2AFC study. Further, the developed simulation method was able to generate wide varieties of clinically observed tumor types. These results provide evidence for the application of this method to 2-D PET imaging applications, and motivate development of this method to generate 3-D PET images.

physics.med-ph

A physics and learning-based transmission-less attenuation compensation method for SPECT

Attenuation compensation (AC) is a pre-requisite for reliable quantification and beneficial for visual interpretation tasks in single-photon emission computed tomography (SPECT). Typical AC methods require the availability of an attenuation map obtained using a transmission scan, such as a CT scan. This has several disadvantages such as increased radiation dose, higher costs, and possible misalignment between SPECT and CT scans. Also, often a CT scan is unavailable. In this context, we and others are showing that scattered photons in SPECT contain information to estimate the attenuation distribution. To exploit this observation, we propose a physics and learning-based method that uses the SPECT emission data in the photopeak and scatter windows to perform transmission-less AC in SPECT. The proposed method uses data acquired in the scatter window to reconstruct an initial estimate of the attenuation map using a physics-based approach. A convolutional neural network is then trained to segment this initial estimate into different regions. Pre-defined attenuation coefficients are assigned to these regions, yielding the reconstructed attenuation map, which is then used to reconstruct the activity map using an ordered subsets expectation maximization-based reconstruction approach. We objectively evaluated the performance of this method using a highly realistic simulation study conducted on the clinically relevant task of detecting perfusion defects in myocardial perfusion SPECT. Our results showed no statistically significant differences between the performance achieved using the proposed method and that with the true attenuation maps. Visually, the images reconstructed using the proposed method looked similar to those with the true attenuation map. Overall, these results provide evidence of the capability of the proposed method to perform transmission-less AC and motivate further evaluation.

physics.med-ph

Bone Material Analogues for PET/MRI Phantoms

Purpose: To develop bone material analogues that can be used in construction of phantoms for simultaneous PET/MRI systems. Methods: Plaster was used as the basis for the bone material analogues tested in this study. It was mixed with varying concentrations of an iodinated CT contrast, a gadolinium-based MR contrast agent, and copper sulfate to modulate the attenuation properties and MRI properties (T1 and T2*). Attenuation was measured with CT and 68Ge transmission scans, and MRI properties were measured with quantitative ultrashort echo time pulse sequences. A proof-of-concept skull was created by plaster casting. Results: Undoped plaster has a 511 keV attenuation coefficient (~0.14 cm-1) similar to cortical bone (0.10-0.15 cm-1), but slightly longer T1 (~500 ms) and T2* (~1.2 ms) MR parameters compared to bone (T1 ~ 300 ms, T2* ~ 0.4 ms). Doping with the iodinated agent resulted in increased attenuation with minimal perturbation to the MR parameters. Doping with a gadolinium chelate greatly reduced T1 and T2*, resulting in extremely short T1 values when the target T2* values were reached, while the attenuation coefficient was unchanged. Doping with copper sulfate was more selective for T2* shortening and achieved comparable T1 and T2* values to bone (after 1 week of drying), while the attenuation coefficient was unchanged. Conclusions: Plaster doped with copper sulfate is a promising bone material analogue for a PET/MRI phantom, mimicking the MR properties (T1 and T2*) and 511 keV attenuation coefficient of human cortical bone.

physics.med-ph

A list-mode OSEM-based attenuation and scatter compensation method for SPECT

Reliable attenuation and scatter compensation (ASC) is a prerequisite for quantification and beneficial for visual interpretation tasks in SPECT. In this paper, we develop a reconstruction method that uses the entire SPECT emission data, i.e. data in both the photopeak and scatter windows, acquired in list-mode format and including the energy attribute of the detected photon, to perform ASC. We implemented a GPU-based version of this method using an ordered subsets expectation maximization (OSEM) algorithm. The method was objectively evaluated using realistic simulation studies on the task of estimating uptake in the striatal regions of the brain in a 2-D dopamine transporter (DaT)-scan SPECT study. We observed that inclusion of data from the scatter window and using list-mode data yielded improved quantification compared to using data only from the photopeak window or using binned data. These results motivate further development of list-mode-based ASC methods that include scatter-window data for SPECT.

physics.med-ph