Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset.

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 'Pre-Pandemic', 28 'Pandemic') using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 ('Pre-Pandemic' cLBP) or between August 2020 and May 2022 ('Pandemic' cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio - DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r's ≥ 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = -0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.

Neuroimmune signatures in chronic low back pain subtypes.

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct 'neuroinflammatory signatures'. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. 'radicular' versus 'axial' back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of 'fibromyalgianess' (i.e. the degree of pain centralization, or 'nociplastic pain'). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of 'neuroinflammatory signatures' that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

Implementation of ISO/IEEE 11073 PHD SpO2 and ECG Device Specializations over Bluetooth HDP following Health Care Profile for Smart Living.

Current m-Health scenarios in the smart living era, as the interpretation of the smart city at each person's level, present several challenges associated with interoperability between different clinical devices and applications. The Continua Health Alliance establishes design guidelines to standardize application communication to guarantee interoperability among medical devices. In this paper, we describe the implementation of two IEEE agents for oxygen saturation level (SpO2) measurements and electrocardiogram (ECG) data acquisition, respectively, and a smartphone IEEE manager for validation. We developed both IEEE agents over the Bluetooth Health Device Profile following the Continua guidelines and they are part of a telemonitoring system. This system was evaluated in a sample composed of 10 volunteers (mean age 29.8 ± 7.1 y/o; 5 females) under supervision of an expert cardiologist. The evaluation consisted of measuring the SpO2 and ECG signal sitting and at rest, before and after exercising for 15 min. Physiological measurements were assessed and compared against commercial devices, and our expert physician did not find any relevant differences in the ECG signal. Additionally, the system was assessed when acquiring and processing different heart rate data to prove that warnings were generated when the heart rate was under/above the thresholds for bradycardia and tachycardia, respectively.

Intracranial Virotherapy for a Canine Hemangioma.

Intracranial hemangiomas are rare neoplastic lesions in dogs that usually appear with life-threatening symptoms. The treatment of choice is tumor resection; however, complete resection is rarely achieved. The patient's prognosis therefore usually worsens due to tumor progression, and adjuvant treatments are required to control the disease. Oncolytic viruses are an innovative approach that lyses the tumor cells and induces immune responses. Here, we report the intratumoral inoculation of ICOCAV15 (an oncolytic adenovirus) in a canine intracranial hemangioma, as adjuvant treatment for incomplete tumor resection. The canine patient showed no side effects, and the tumor volume decreased over the 12 months after the treatment, as measured by magnetic resonance imaging using volumetric criteria. When progressive disease was detected at month 18, a new dose of ICOCAV15 was administered. The patient died 31.9 months after the first inoculation of the oncolytic adenovirus. Furthermore, tumor-infiltrated immune cells increased in number after the viral administrations, suggesting tumor microenvironment activation. The increased number of infiltrated immune cells, the long survival time and the absence of side effects suggest that ICOCAV15 could be a safe and effective treatment and should be further explored as a novel therapy for canine hemangiomas.

Individualized SAR calculations using computer vision-based MR segmentation and a fast electromagnetic solver.

PURPOSE: We propose a fast, patient-specific workflow for on-line specific absorption rate (SAR) supervision. An individualized electromagnetic model is created while the subject is on the table, followed by rapid SAR estimates for that individual. Our goal is an improved correspondence between the patient and model, reducing reliance on general anatomical body models. METHODS: A 3D fat-water 3T acquisition (~2 minutes) is automatically segmented using a computer vision algorithm (~1 minute) into what we found to be the most important electromagnetic tissue classes: air, bone, fat, and soft tissues. We then compute the individual's EM field exposure and global and local SAR matrices using a fast electromagnetic integral equation solver. We assess the approach in 10 volunteers and compare to the SAR seen in a standard generic body model (Duke). RESULTS: The on-the-table workflow averaged 7'44″. Simulation of the simplified Duke models confirmed that only air, bone, fat, and soft tissue classes are needed to estimate global and local SAR with an error of 6.7% and 2.7%, respectively, compared to the full model. In contrast, our volunteers showed a 16.0% and 20.3% population variability in global and local SAR, respectively, which was mostly underestimated by the Duke model. CONCLUSION: Timely construction and deployment of a patient-specific model is computationally feasible. The benefit of resolving the population heterogeneity compared favorably to the modest modeling error incurred. This suggests that individualized SAR estimates can improve electromagnetic safety in MRI and possibly reduce conservative safety margins that account for patient-model mismatch, especially in non-standard patients.

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

BACKGROUND: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use. METHODS: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered. RESULTS: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies. CONCLUSION: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.

Striatal hypofunction as a neural correlate of mood alterations in chronic pain patients.

BACKGROUND: Chronic pain and mood disorders share common neuroanatomical substrates involving disruption of the reward system. Although increase in negative affect (NA) and decrease in positive affect (PA) are well-known factors complicating the clinical presentation of chronic pain patients, our understanding of the mechanisms underlying the interaction between pain and PA/NA remains limited. Here, we used a validated task probing behavioral and neural responses to monetary rewards and losses in conjunction with functional magnetic resonance imaging (fMRI) to test the hypothesis that dysfunction of the striatum, a key mesolimbic structure involved in the encoding of motivational salience, relates to mood alterations comorbid with chronic pain. METHODS: Twenty-eight chronic musculoskeletal pain patients (chronic low back pain, n=15; fibromyalgia, n=13) and 18 healthy controls underwent fMRI while performing the Monetary Incentive Delay (MID) task. Behavioral and neural responses were compared across groups and correlated against measures of depression (Beck Depression Inventory) and hedonic capacity (Snaith-Hamilton Pleasure Scale). RESULTS: Compared to controls, patients demonstrated higher anhedonia and depression scores, and a dampening of striatal activation and incentive-related behavioral facilitation (reduction in reaction times) during reward and loss trials of the MID task (ps â€‹< â€‹0.05). In all participants, lower activation of the right striatum during reward trials was correlated with lower incentive-related behavioral facilitation and higher anhedonia scores (ps â€‹< â€‹0.05). Finally, among patients, lower bilateral striatal activation during loss trials was correlated with higher depression scores (ps â€‹< â€‹0.05). CONCLUSIONS: In chronic pain, PA reduction and NA increase are accompanied by striatal hypofunction as measured by the MID task.

Resting-state connectivity and network parameter analysis in alcohol-dependent males. A simultaneous EEG-MEG study.

There is supporting evidence of alcohol negative effects on the brain: neuroimaging and psychophysiological studies finding anatomical and functional connectivity (FC) changes associated with the dependence process. Thus, the aim of this work was to evaluate brain FC and network characteristics of alcohol-dependent individuals in resting state. For this study, we included males diagnosed with alcohol dependence (N = 25) and a group of healthy individuals (N = 23). Simultaneous EEG-MEG (electroencephalographic and magnetoencephalographic) activity was recorded in 5 min of eyes-closed resting state. EEG-MEG activity was preprocessed and FC was computed through the leakage-corrected version of phase locking value (ciPLV). Additionally, local (degree, efficiency, clustering) and global (efficiency, characteristic path length) network parameters were computed. Connectivity analysis showed an increase in phase-lagged synchronization, mainly between frontal and frontotemporal regions, in high beta band, and a decrease in interhemispheric gamma, for alcohol-dependent individuals. Network analysis revealed intergroup differences at the local level for high beta, indicating higher degree, clustering, and efficiency, mostly at frontal nodes, together with a decrease in these measures at more posterior sites for patients' group. The hyper-synchronization in beta, next to the hypo-synchronization in gamma, could indicate an alteration in communication between hemispheres, but also a possible functional compensation mechanism in neural circuits. This could be also supported by network characteristic data, where local alterations in communication are observed.

In vivo human head MRI at 10.5T: A radiofrequency safety study and preliminary imaging results.

PURPOSE: The purpose of this study is to safely acquire the first human head images at 10.5T. METHODS: To ensure safety of subjects, we validated the electromagnetic simulation model of our coil. We obtained quantitative agreement between simulated and experimental B1+ and specific absorption rate (SAR). Using the validated coil model, we calculated radiofrequency power levels to safely image human subjects. We conducted all experiments and imaging sessions in a controlled radiofrequency safety lab and the whole-body 10.5T scanner in the Center for Magnetic Resonance Research. RESULTS: Quantitative agreement between the simulated and experimental results was obtained including S-parameters, B1+ maps, and SAR. We calculated peak 10 g average SAR using 4 different realistic human body models for a quadrature excitation and demonstrated that the peak 10 g SAR variation between subjects was less than 30%. We calculated safe power limits based on this set and used those limits to acquire T2 - and T2∗ -weighted images of human subjects at 10.5T. CONCLUSIONS: In this study, we acquired the first in vivo human head images at 10.5T using an 8-channel transmit/receive coil. We implemented and expanded a previously proposed workflow to validate the electromagnetic simulation model of the 8-channel transmit/receive coil. Using the validated coil model, we calculated radiofrequency power levels to safely image human subjects.

Radiofrequency heating studies on anesthetized swine using fractionated dipole antennas at 10.5 T.

PURPOSE: To validate electromagnetic and thermal simulations with in vivo temperature measurements, and to demonstrate a framework that can be used to predict temperature increase caused by radiofrequency (RF) excitation with dipole transmitter arrays. METHODS: Dipole arrays were used to deliver RF energy in the back/neck region of the swine using different RF excitation patterns (n = 2-4 per swine) for heating. The temperature in anesthetized swine (n = 3) was measured using fluoroscopic probes (n = 12) and compared against thermal modeling from animal-specific electromagnetic simulations. RESULTS: Simulated temperature curves were in agreement with the measured data. The root mean square error between simulated and measured temperature rise at all locations (at the end of each RF excitation) is calculated as 0.37°C. The mean experimental temperature rise at the maximum temperature rise locations (averaged over all experiments) is calculated as 2.89°C. The root mean square error between simulated and measured temperature at the maximum temperature rise location is calculated as 0.57°C. (Error values are averaged over all experiments.) CONCLUSIONS: Electromagnetic and thermal simulations were validated with experiments. Thermal effects of RF excitation at 10.5 Tesla with dipoles were investigated. Magn Reson Med 79:479-488, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Robust time-shifted spoke pulse design in the presence of large B0 variations with simultaneous reduction of through-plane dephasing, B1+ effects, and the specific absorption rate using parallel transmission.

PURPOSE: To design parallel transmission spokes pulses with time-shifted profiles for joint mitigation of intensity variations due to B1+ effects, signal loss due to through-plane dephasing, and the specific absorption rate (SAR) at 7T. METHODS: We derived a slice-averaged small tip angle (SA-STA) approximation of the magnetization signal at echo time that depends on the B1+ transmit profiles, the through-slice B0 gradient and the amplitude and time-shifts of the spoke waveforms. We minimize a magnitude least-squares objective based on this signal equation using a fast interior-point approach with analytical expressions of the Jacobian and Hessian. RESULTS: Our algorithm runs in less than three minutes for the design of two-spoke pulses subject to hundreds of local SAR constraints. On a B0/B1+ head phantom, joint optimization of the channel-dependent time-shifts and spoke amplitudes allowed signal recovery in high-B0 regions at no increase of SAR. Although the method creates uniform magnetization profiles (ie, uniform intensity), the flip angle varies across the image, which makes it ill-suited to T1-weighted applications. CONCLUSIONS: The SA-STA approach presented in this study is best suited to T2*-weighted applications with long echo times that require signal recovery around high B0 regions. Magn Reson Med 76:540-554, 2016. © 2015 Wiley Periodicals, Inc.

Multi-atlas and label fusion approach for patient-specific MRI based skull estimation.

PURPOSE: MRI-based skull segmentation is a useful procedure for many imaging applications. This study describes a methodology for automatic segmentation of the complete skull from a single T1-weighted volume. METHODS: The skull is estimated using a multi-atlas segmentation approach. Using a whole head computed tomography (CT) scan database, the skull in a new MRI volume is detected by nonrigid image registration of the volume to every CT, and combination of the individual segmentations by label-fusion. We have compared Majority Voting, Simultaneous Truth and Performance Level Estimation (STAPLE), Shape Based Averaging (SBA), and the Selective and Iterative Method for Performance Level Estimation (SIMPLE) algorithms. RESULTS: The pipeline has been evaluated quantitatively using images from the Retrospective Image Registration Evaluation database (reaching an overlap of 72.46 ± 6.99%), a clinical CT-MR dataset (maximum overlap of 78.31 ± 6.97%), and a whole head CT-MRI pair (maximum overlap 78.68%). A qualitative evaluation has also been performed on MRI acquisition of volunteers. CONCLUSION: It is possible to automatically segment the complete skull from MRI data using a multi-atlas and label fusion approach. This will allow the creation of complete MRI-based tissue models that can be used in electromagnetic dosimetry applications and attenuation correction in PET/MR.

SAR reduction in 7T C-spine imaging using a "dark modes" transmit array strategy.

PURPOSE: Local specific absorption rate (SAR) limits many applications of parallel transmit (pTx) in ultra high-field imaging. In this Note, we introduce the use of an array element, which is intentionally inefficient at generating spin excitation (a "dark mode") to attempt a partial cancellation of the electric field from those elements that do generate excitation. We show that adding dipole elements oriented orthogonal to their conventional orientation to a linear array of conventional loop elements can lower the local SAR hotspot in a C-spine array at 7 T. METHODS: We model electromagnetic fields in a head/torso model to calculate SAR and excitation B1 (+) patterns generated by conventional loop arrays and loop arrays with added electric dipole elements. We utilize the dark modes that are generated by the intentional and inefficient orientation of dipole elements in order to reduce peak 10g local SAR while maintaining excitation fidelity. RESULTS: For B1 (+) shimming in the spine, the addition of dipole elements did not significantly alter the B1 (+) spatial pattern but reduced local SAR by 36%. CONCLUSION: The dipole elements provide a sufficiently complimentary B1 (+) and electric field pattern to the loop array that can be exploited by the radiofrequency shimming algorithm to reduce local SAR.

Parallel transmit pulse design for patients with deep brain stimulation implants.

PURPOSE: Specific absorption rate (SAR) amplification around active implantable medical devices during diagnostic MRI procedures poses a potential risk for patient safety. In this study, we present a parallel transmit (pTx) strategy that can be used to safely scan patients with deep brain stimulation (DBS) implants. METHODS: We performed electromagnetic simulations at 3T using a uniform phantom and a multitissue realistic head model with a generic DBS implant. Our strategy is based on using implant-friendly modes, which are defined as the modes of an array that reduce the local SAR around the DBS lead tip. These modes are used in a spokes pulse design algorithm in order to produce highly uniform magnitude least-squares flip angle excitations. RESULTS: Local SAR (1 g) at the lead tip is reduced below 0.1 W/kg compared with 31.2 W/kg, which is obtained by a simple quadrature birdcage excitation without any sort of SAR mitigation. For the multitissue realistic head model, peak 10 g local SAR and global SAR are obtained as 4.52 W/kg and 0.48 W/kg, respectively. A uniform axial flip angle is also obtained (NRMSE <3%). CONCLUSION: Parallel transmit arrays can be used to generate implant-friendly modes and to reduce SAR around DBS implants while constraining peak local SAR and global SAR and maximizing flip angle homogeneity.

A case study of medical image software evolution and its impact in the medical imaging community.

Objective: We present the evolution of medical imaging software and its impact on the medical imaging community through the study of four open-source image analysis software platforms: 3D Slicer, FreeSurfer, FSL, and SPM. Materials and methods: We have studied the impact of these software tools over time, measured by the number of scientific citations. Additionally, we have also studied the source code evolution by measuring the lines of code and the tarball size of the stable releases and the changes in programming languages. Results and discussion: The rising number of related scientific publications confirms the popularity of these software tools in the research community, albeit some differences can be observed in the popularity of the tools. Moreover, we demonstrate that source code has evolved to modernize and optimize, at least partially thanks to the collaboration and code sharing with the user community. Furthermore, this evolution reveals an increased use of higher-level programming languages and meta-languages. Conclusions: The study of four open-source packages has revealed certain patterns in the evolution of medical imaging software and their impact on the medical image community. Further analyses and complementary metrics are suggested.

Enhancing adaptive proton therapy through CBCT images: Synthetic head and neck CT generation based on 3D vision transformers.

BACKGROUND: Proton therapy is a form of radiotherapy commonly used to treat various cancers. Due to its high conformality, minor variations in patient anatomy can lead to significant alterations in dose distribution, making adaptation crucial. While cone-beam computed tomography (CBCT) is a well-established technique for adaptive radiation therapy (ART), it cannot be directly used for adaptive proton therapy (APT) treatments because the stopping power ratio (SPR) cannot be estimated from CBCT images. PURPOSE: To address this limitation, Deep Learning methods have been suggested for converting pseudo-CT (pCT) images from CBCT images. In spite of convolutional neural networks (CNNs) have shown consistent improvement in pCT literature, there is still a need for further enhancements to make them suitable for clinical applications. METHODS: The authors introduce the 3D vision transformer (ViT) block, studying its performance at various stages of the proposed architectures. Additionally, they conduct a retrospective analysis of a dataset that includes 259 image pairs from 59 patients who underwent treatment for head and neck cancer. The dataset is partitioned into 80% for training, 10% for validation, and 10% for testing purposes. RESULTS: The SPR maps obtained from the pCT using the proposed method present an absolute relative error of less than 5% from those computed from the planning CT, thus improving the results of CBCT. CONCLUSIONS: We introduce an enhanced ViT3D architecture for pCT image generation from CBCT images, reducing SPR error within clinical margins for APT workflows. The new method minimizes bias compared to CT-based SPR estimation and dose calculation, signaling a promising direction for future research in this field. However, further research is needed to assess the robustness and generalizability across different medical imaging applications.

Thalamic neurometabolite alterations in chronic low back pain: a common phenomenon across musculoskeletal pain conditions?

ABSTRACT: Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also be observed in patients with a different musculoskeletal condition, such as chronic low back pain (cLBP). Thirty-six patients with cLBP and 20 healthy controls were scanned using 1 H-magnetic resonance spectroscopy (MRS) and a PRESS (Point RESolved Spectroscopy) sequence with voxel placement in the left thalamus. Compared with healthy controls, patients with cLBP demonstrated lower absolute concentrations of NAA ( P = 0.0005) and Cho ( P < 0.05) and higher absolute concentrations of mIns ( P = 0.01) when controlling for age, as predicted by our previous work in KOA. In contrast to our KOA study, mIns levels in this population did not significantly correlate with pain measures (eg, pain severity or duration). However, exploratory analyses revealed that NAA levels in patients were negatively correlated with the severity of sleep disturbance ( P < 0.01), which was higher in patients compared with healthy controls ( P < 0.001). Additionally, also in patients, both Cho and mIns levels were positively correlated with age ( P < 0.01 and P < 0.05, respectively). Altogether, these results suggest that thalamic metabolite changes may be common across etiologically different musculoskeletal chronic pain conditions, including cLBP and KOA, and may relate to symptoms often comorbid with chronic pain, such as sleep disturbance. The functional and clinical significance of these brain changes remains to be fully understood.

Exploring dual energy CT synthesis in CBCT-based adaptive radiotherapy and proton therapy: application of denoising diffusion probabilistic models.

BACKGROUND: Adaptive radiotherapy (ART) requires precise tissue characterization to optimize treatment plans and enhance the efficacy of radiation delivery while minimizing exposure to organs at risk (OAR). Traditional imaging techniques such as cone beam computed tomography (CBCT) used in ART settings often lack the resolution and detail necessary for accurate dosimetry, especially in proton therapy. Purpose: This study aims to enhance ART by introducing an innovative approach that synthesizes dual-energy computed tomography (DECT) images from CBCT scans using a novel 3D conditional denoising diffusion probabilistic model (DDPM) multi-decoder. This method seeks to improve dose calculations in ART planning, enhancing tissue characterization. Methods: We utilized a paired CBCT-DECT dataset from 54 head and neck cancer patients to train and validate our DDPM model. The model employs a multi-decoder Swin-UNET architecture that synthesizes high-resolution DECT images by progressively reducing noise and artifacts in CBCT scans through a controlled diffusion process. Results: The proposed method demonstrated superior performance in synthesizing DECT images (High DECT MAE 39.582 ± 0.855 and Low DECT MAE 48.540± 1.833) with significantly enhanced signal-to-noise ratio and reduced artifacts compared to traditional GAN-based methods. It showed marked improvements in tissue characterization and anatomical structure similarity, critical for precise proton and radiation therapy planning. Conclusions: This research has opened a new avenue in CBCT-CT synthesis for ART/APT by generating DECT images using an enhanced DDPM approach. The demonstrated similarity between the synthesized DECT images and ground truth images suggests that these synthetic volumes can be used for accurate dose calculations, leading to better adaptation in treatment planning.

Material decomposition maps based calibration of dual energy CT scanners for proton therapy planning: a phantom study.

We introduce a new calibration method for dual energy CT (DECT) based on material decomposition (MD) maps, specifically iodine and water MD maps. The aim of this method is to provide the first DECT calibration based on MD maps. The experiments were carried out using a general electric (GE) revolution CT scanner with ultra-fast kV switching and used a density phantom by GAMMEX for calibration and evaluation. The calibration process involves several steps. First, we tested the ability of MD values to reproduce Hounsfield unit (HU) values of single energy CT (SECT) acquisitions and it was found that the errors were below 1%, validating their use for HU reproduction. Next, the different definitions of computedZvalues were compared and the robustness of the approach based on the materials' composition was confirmed. Finally, the calibration method was compared with a previous method by Bourqueet al, providing a similar level of accuracy and superior performance in terms of precision. Overall, this novel DECT calibration method offers improved accuracy and reliability in determining tissue-specific physical properties. The resulting maps can be valuable for proton therapy treatments, where precise dose calculations and accurate tissue differentiation are crucial for optimal treatment planning and delivery.

[ 11 C]-PBR28 positron emission tomography signal as an imaging marker of joint inflammation in knee osteoarthritis.

ABSTRACT: Although inflammation is known to play a role in knee osteoarthritis (KOA), inflammation-specific imaging is not routinely performed. In this article, we evaluate the role of joint inflammation, measured using [ 11 C]-PBR28, a radioligand for the inflammatory marker 18-kDa translocator protein (TSPO), in KOA. Twenty-one KOA patients and 11 healthy controls (HC) underwent positron emission tomography/magnetic resonance imaging (PET/MRI) knee imaging with the TSPO ligand [ 11 C]-PBR28. Standardized uptake values were extracted from regions-of-interest (ROIs) semiautomatically segmented from MRI data, and compared across groups (HC, KOA) and subgroups (unilateral/bilateral KOA symptoms), across knees (most vs least painful), and against clinical variables (eg, pain and Kellgren-Lawrence [KL] grades). Overall, KOA patients demonstrated elevated [ 11 C]-PBR28 binding across all knee ROIs, compared with HC (all P 's < 0.005). Specifically, PET signal was significantly elevated in both knees in patients with bilateral KOA symptoms (both P 's < 0.01), and in the symptomatic knee ( P < 0.05), but not the asymptomatic knee ( P = 0.95) of patients with unilateral KOA symptoms. Positron emission tomography signal was higher in the most vs least painful knee ( P < 0.001), and the difference in pain ratings across knees was proportional to the difference in PET signal ( r = 0.74, P < 0.001). Kellgren-Lawrence grades neither correlated with PET signal (left knee r = 0.32, P = 0.19; right knee r = 0.18, P = 0.45) nor pain ( r = 0.39, P = 0.07). The current results support further exploration of [ 11 C]-PBR28 PET signal as an imaging marker candidate for KOA and a link between joint inflammation and osteoarthritis-related pain severity.