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.

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.

Development of a Super-Resolution Scheme for Pediatric Magnetic Resonance Brain Imaging Through Convolutional Neural Networks.

Pediatric medical imaging represents a real challenge for physicians, as children who are patients often move during the examination, and it causes the appearance of different artifacts in the images. Thus, it is not possible to obtain good quality images for this target population limiting the possibility of evaluation and diagnosis in certain pathological conditions. Specifically, magnetic resonance imaging (MRI) is a technique that requires long acquisition times and, therefore, demands the use of sedation or general anesthesia to avoid the movement of the patient, which is really damaging in this specific population. Because ALARA (as low as reasonably achievable) principles should be considered for all imaging studies, one of the most important reasons for establishing novel MRI imaging protocols is to avoid the harmful effects of anesthesia/sedation. In this context, ground-breaking concepts and novel technologies, such as artificial intelligence, can help to find a solution to these challenges while helping in the search for underlying disease mechanisms. The use of new MRI protocols and new image acquisition and/or pre-processing techniques can aid in the development of neuroimaging studies for children evaluation, and their translation to pediatric populations. In this paper, a novel super-resolution method based on a convolutional neural network (CNN) in two and three dimensions to automatically increase the resolution of pediatric brain MRI acquired in a reduced time scheme is proposed. Low resolution images have been generated from an original high resolution dataset and used as the input of the CNN, while several scaling factors have been assessed separately. Apart from a healthy dataset, we also tested our model with pathological pediatric MRI, and it successfully recovers the original image quality in both visual and quantitative ways, even for available examples of dysplasia lesions. We hope then to establish the basis for developing an innovative free-sedation protocol in pediatric anatomical MRI acquisition.

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.

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.

PET/MRI and PET/CT Radiomics in Primary Cervical Cancer: A Pilot Study on the Correlation of Pelvic PET, MRI, and CT Derived Image Features.

PURPOSE: To evaluate the correlation of radiomic features in pelvic [2-deoxy-2-18F]fluoro-D-glucose positron emission tomography/magnetic resonance imaging and computed tomography ([18F]FDG PET/MRI and [18F]FDG PET/CT) in patients with primary cervical cancer (CCa). PROCEDURES: Nineteen patients with histologically confirmed primary squamous cell carcinoma of the cervix underwent same-day [18F]FDG PET/MRI and PET/CT. Two nuclear medicine physicians performed a consensus reading in random order. Free-hand regions of interest covering the primary cervical tumors were drawn on PET, contrast-enhanced pelvic CT, and pelvic MR (T2 weighted and ADC) images. Several basic imaging features, standard uptake values (SUVmean, SUVmax, and SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and more advanced texture analysis features were calculated. Pearson's correlation test was used to assess the correlation between each pair of features. Features were compared between local and metastatic tumors, and their role in predicting metastasis was evaluated by receiver operating characteristic curves. RESULTS: For a total of 101 extracted features, 1104/5050 pairs of features showed a significant correlation (ρ ≥ 0.70, p < 0.05). There was a strong correlation between 190/484 PET pairs of features from PET/MRI and PET/CT, 91/418 pairs of CT and PET from PET/CT, 79/418 pairs of T2 and PET from PET/MRI, and 50/418 pairs of ADC and PET from PET/MRI. Significant difference was seen between eight features in local and metastatic tumors including MTV, TLG, and entropy on PET from PET/CT; MTV and TLG on PET from PET/MRI; compactness and entropy on T2; and entropy on ADC images. CONCLUSIONS: We demonstrated strong correlation of many extracted radiomic features between PET/MRI and PET/CT. Eight radiomic features calculated on PET/CT and PET/MRI were significantly different between local and metastatic CCa. This study paves the way for future studies to evaluate the diagnostic and predictive potential of radiomics that could guide clinicians toward personalized patients care.

3D magnetic resonance spectroscopic imaging reveals links between brain metabolites and multidimensional pain features in fibromyalgia.

BACKGROUND: Fibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood. METHODS: We applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro-metabolite (e.g. combined glutamate and glutamine, Glx; myo-inositol, mIno; and combined (total) N-acetylaspartate and N-acetylaspartylglutamate, tNAA) levels and multidimensional clinical/behavioural variables (e.g. pain catastrophizing, clinical pain severity and evoked pain sensitivity) in women with fibromyalgia (N = 87). RESULTS: Pain catastrophizing scores were positively correlated with Glx and tNAA levels in insular cortex, and negatively correlated with mIno levels in posterior cingulate cortex (PCC). Clinical pain severity was positively correlated with Glx levels in insula and PCC, and with tNAA levels in anterior midcingulate cortex (aMCC), but negatively correlated with mIno levels in aMCC and thalamus. Evoked pain sensitivity was negatively correlated with levels of tNAA in insular cortex, MCC, PCC and thalamus. CONCLUSIONS: These findings support single voxel placement targeting nociceptive processing areas in prior 1 H-MRS studies, but also highlight other areas not as commonly targeted, such as PCC, as important for chronic pain pathophysiology. Identifying target brain regions linked to multidimensional symptoms of fibromyalgia (e.g. negative cognitive/affective response to pain, clinical pain, evoked pain sensitivity) may aid the development of neuromodulatory and individualized therapies. Furthermore, efficient multi-region sampling with 3D MRSI could reduce the burden of lengthy scan time for clinical research applications of molecular brain-based mechanisms supporting multidimensional aspects of fibromyalgia. SIGNIFICANCE: This large N study linked brain metabolites and pain features in fibromyalgia patients, with a better spatial resolution and brain coverage, to understand a molecular mechanism underlying pain catastrophizing and other aspects of pain transmission. Metabolite levels in self-referential cognitive processing area as well as pain-processing regions were associated with pain outcomes. These results could help the understanding of its pathophysiology and treatment strategies for clinicians.

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.

The Role of Inflammation after Surgery for Elders (RISE) study: Examination of [11C]PBR28 binding and exploration of its link to post-operative delirium.

Major surgery is associated with a systemic inflammatory cascade that is thought, in some cases, to contribute to transient and/or sustained cognitive decline, possibly through neuroinflammatory mechanisms. However, the relationship between surgery, peripheral and central nervous system inflammation, and post-operative cognitive outcomes remains unclear in humans, primarily owing to limitations of in vivo biomarkers of neuroinflammation which vary in sensitivity, specificity, validity, and reliability. In the present study, [11C]PBR28 positron emission tomography, cerebrospinal fluid (CSF), and blood plasma biomarkers of inflammation were assessed pre-operatively and 1-month post-operatively in a cohort of patients (N = 36; 30 females; ≥70 years old) undergoing major orthopedic surgery under spinal anesthesia. Delirium incidence and severity were evaluated daily during hospitalization. Whole-brain voxel-wise and regions-of-interest analyses were performed to determine the magnitude and spatial extent of changes in [11C]PBR28 uptake following surgery. Results demonstrated that, compared with pre-operative baseline, [11C]PBR28 binding in the brain was globally downregulated at 1 month following major orthopedic surgery, possibly suggesting downregulation of the immune system of the brain. No significant relationship was identified between post-operative delirium and [11C]PBR28 binding, possibly due to a small number (n = 6) of delirium cases in the sample. Additionally, no significant relationships were identified between [11C]PBR28 binding and CSF/plasma biomarkers of inflammation. Collectively, these results contribute to the literature by demonstrating in a sizeable sample the effect of major surgery on neuroimmune activation and preliminary evidence identifying no apparent associations between [11C]PBR28 binding and fluid inflammatory markers or post-operative delirium.

PET/MRI Radiomics in Rectal Cancer: a Pilot Study on the Correlation Between PET- and MRI-Derived Image Features with a Clinical Interpretation.

PURPOSE: The aim of this study was to explore possible correlations among different imaging features from 2-deoxy-2-[18F]fluoro-D-Glucose positron emission tomography/magnetic resonance imaging (PET/MRI) in rectal cancer (RC). PROCEDURES: RC patients who underwent PET/MRI were enrolled. A region of interest (ROI) was drawn around each primary RC on PET/MRI images (PET, pelvic axial T2w, and apparent diffusion coefficient maps (ADC)). Multiple imaging features were assessed, and Pearson's correlation was used to explore possible correlations among them. RESULTS: A total of 13 patients were included, mean age 56.1 years old, 6 females. A strong inverse correlation was observed between SUVpeak and ADCmean values, MTV and T2 sphericity, MTV and ADC sphericity, MTV and T2 entropy, and TLG and ADC sphericity. There was also strong direct correlation between PET entropy and ADC sphericity. CONCLUSIONS: In conclusion, several clinically relevant correlations were observed between PET and MRI imaging features. These findings show how the use of both modalities provides complementary information.

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.

Dixon-VIBE Deep Learning (DIVIDE) Pseudo-CT Synthesis for Pelvis PET/MR Attenuation Correction.

Whole-body attenuation correction (AC) is still challenging in combined PET/MR scanners. We describe Dixon-VIBE Deep Learning (DIVIDE), a deep-learning network that allows synthesizing pelvis pseudo-CT maps based only on the standard Dixon volumetric interpolated breath-hold examination (Dixon-VIBE) images currently acquired for AC in some commercial scanners. Methods: We propose a network that maps between the four 2-dimensional (2D) Dixon MR images (water, fat, in-phase, and out-of-phase) and their corresponding 2D CT image. In contrast to previous methods, we used transposed convolutions to learn the up-sampling parameters, we used whole 2D slices to provide context information, and we pretrained the network with brain images. Twenty-eight datasets obtained from 19 patients who underwent PET/CT and PET/MR examinations were used to evaluate the proposed method. We assessed the accuracy of the µ-maps and reconstructed PET images by performing voxel- and region-based analysis comparing the SUVs (in g/mL) obtained after AC using the Dixon-VIBE (PETDixon), DIVIDE (PETDIVIDE), and CT-based (PETCT) methods. Additionally, the bias in quantification was estimated in synthetic lesions defined in the prostate, rectum, pelvis, and spine. Results: Absolute mean relative change values relative to CT AC were lower than 2% on average for the DIVIDE method in every region of interest except for bone tissue, where it was lower than 4% and 6.75 times smaller than the relative change of the Dixon method. There was an excellent voxel-by-voxel correlation between PETCT and PETDIVIDE (R2 = 0.9998, P < 0.01). The Bland-Altman plot between PETCT and PETDIVIDE showed that the average of the differences and the variability were lower (mean PETCT-PETDIVIDE SUV, 0.0003; PETCT-PETDIVIDE SD, 0.0094; 95% confidence interval, [-0.0180,0.0188]) than the average of differences between PETCT and PETDixon (mean PETCT-PETDixon SUV, 0.0006; PETCT-PETDixon SD, 0.0264; 95% confidence interval, [-0.0510,0.0524]). Statistically significant changes in PET data quantification were observed between the 2 methods in the synthetic lesions, with the largest improvement in femur and spine lesions. Conclusion: The DIVIDE method can accurately synthesize a pelvis pseudo-CT scan from standard Dixon-VIBE images, allowing for accurate AC in combined PET/MR scanners. Additionally, our implementation allows rapid pseudo-CT synthesis, making it suitable for routine applications and even allowing retrospective processing of Dixon-VIBE data.

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.