Breast imaging with an ultra-low field MRI scanner: a pilot study.

Breast cancer screening is necessary to reduce mortality due to undetected breast cancer. Current methods have limitations, and as a result many women forego regular screening. Magnetic resonance imaging (MRI) can overcome most of these limitations, but access to conventional MRI is not widely available for routine annual screening. Here, we used an MRI scanner operating at ultra-low field (ULF) to image the left breasts of 11 women (mean age, 35 years ±13 years) in the prone position. Three breast radiologists reviewed the imaging and were able to discern the breast outline and distinguish fibroglandular tissue (FGT) from intramammary adipose tissue. Additionally, the expert readers agreed on their assessment of the breast tissue pattern including fatty, scattered FGT, heterogeneous FGT, and extreme FGT. This preliminary work demonstrates that ULF breast MRI is feasible and may be a potential option for comfortable, widely deployable, and low-cost breast cancer diagnosis and screening.

Mitoxantrone encapsulated photosensitizer nanomicelle as carrier-free theranostic nanomedicine for near-infrared fluorescence imaging-guided chemo-photodynamic combination therapy on cancer.

Combination therapy exhibits higher efficacy than any single therapy, inspiring various nanocarrier-assisted multi-drug co-delivery systems for the combined treatment of cancer. However, most nanocarriers are inert and non-therapeutic and have potential side effects. Herein, an amphiphilic polymer composed of a hydrophobic photosensitizer and hydrophilic poly(ethylene glycol) was employed as the nanocarriers and photosensitizers to encapsulate the chemotherapeutic drug mitoxantrone for chemo-photodynamic combination therapy. The resulting nanodrug consisted solely of pharmacologically active ingredients, thus avoiding potential toxicity induced by inert excipients. This multifunctional nanoplatform demonstrated significantly superior treatment performance compared to monotherapy for colorectal cancer, both in vitro and in vivo, achieving near-infrared fluorescence imaging-mediated chemo-photodynamic combined eradication of malignancy.

Global democratisation of proton radiotherapy.

Proton radiotherapy is an advanced treatment option compared with conventional x-ray treatment, delivering much lower doses of radiation to healthy tissues surrounding the tumour. However, proton therapy is currently not widely available. In this Review, we summarise the evolution of proton therapy to date, together with the benefits to patients and society. These developments have led to an exponential growth in the number of hospitals using proton radiotherapy worldwide. However, the gap between the number of patients who should be treated with proton radiotherapy and those who have access to it remains large. We summarise the ongoing research and development that is contributing to closing this gap, including the improvement of treatment efficiency and efficacy, and advances in fixed-beam treatments that do not require an enormously large, heavy, and costly gantry. The ultimate goal of decreasing the size of proton therapy machines to fit into standard treatment rooms appears to be within reach, and we discuss future research and development opportunities to achieve this goal.

Untargeted metabolomics analysis in drug-naïve patients with severe obsessive-compulsive disorder.

Introduction: Obsessive-compulsive disorder (OCD), characterized by the presence of obsessions and/or compulsions, is often difficult to diagnose and treat in routine clinical practice. The candidate circulating biomarkers and primary metabolic pathway alteration of plasma in OCD remain poorly understood. Methods: We recruited 32 drug-naïve patients with severe OCD and 32 compared healthy controls and applied the untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to assess their circulating metabolic profiles. Both univariate and multivariate analyses were then utilized to filtrate differential metabolites between patients and healthy controls, and weighted Correlation Network Analysis (WGCNA) was utilized to screen out hub metabolites. Results: A total of 929 metabolites were identified, including 34 differential metabolites and 51 hub metabolites, with an overlap of 13 metabolites. Notably, the following enrichment analyses underlined the importance of unsaturated fatty acids and tryptophan metabolism alterations in OCD. Metabolites of these pathways in plasma appeared to be promising biomarkers, such as Docosapentaenoic acid and 5-Hydroxytryptophan, which may be biomarkers for OCD identification and prediction of sertraline treatment outcome, respectively. Conclusion: Our findings revealed alterations in the circulating metabolome and the potential utility of plasma metabolites as promising biomarkers in OCD.

Our journeys through the fascinating world of proton radiation therapy.

The purpose of this article is to share the excitement of the science of proton therapy, told by two physicists, who started their career in this area at different times. The authors' journey spans the evolution of proton therapy over the past 30 years, taking the reader from the time when it was an extremely exotic treatment modality until its more common use today. Over this time period, the authors' research and development aimed at an improved understanding of the physical benefits of intensity-modulated proton therapy and arc therapy, treatment planning and optimization to take proton-specific uncertainties into account, and imaging to measure the proton range in the patient. The final section focuses on emerging themes to democratize proton therapy by substantially reducing its size and price, for much greater affordability and global availability of this treatment modality.

Technical note: Does the greater power of pencil beam scanning reduce the need for a proton gantry? A study of head-and-neck and brain tumors.

PURPOSE: Proton therapy systems without a gantry can be more compact and less expensive in terms of capital cost and therefore more available to a larger patient population. Would the advances in pencil beam scanning (PBS) and robotics make gantry-less treatment possible? In this study, we explore if the high-quality treatment plans can be obtained without a gantry. METHODS AND MATERIALS: We recently showed that proton treatments with the patient in an upright position may be feasible with a new soft robotic immobilization device and imaging which enables multiple possible patient orientations during a treatment. In this study, we evaluate if this new treatment geometry could enable high quality treatment plans without a gantry. We created PBS treatment plans for seven patients with head-and-neck or brain tumors. Each patient was planned with two scenarios: one with a gantry with the patient in supine position and the other with a gantry-less fixed horizontal beam-line with the patient sitting upright. For the treatment plans, dose-volume-histograms (DVHs), target homogeneity index (HI), mean dose, D 2 ${D_2}$ , and D 98 ${D_{98}}$ are reported. A robustness analysis of one plan was performed with ± $ \pm $ 2.5-mm setup errors and ± $ \pm $ 3.5% range uncertainties with nine scenarios. RESULTS: Most of the PBS-gantry-less plans had similar target HI and organs-at-risk mean dose as compared to PBS-gantry plans and similar robustness with respect to range uncertainties and setup errors. CONCLUSIONS: PBS provides sufficient power to deliver high quality treatment plans without requiring a gantry for head-and-neck or brain tumors. In combination with the development of the new positioning and immobilization methods required to support this treatment geometry, this work suggests the feasibility of further development of a compact proton therapy system with a fixed horizontal beam-line to treat patients in sitting and reclined positions.

Effect of anthracycline-based postoperative chemotherapy on blood glucose and lipid profiles in patients with invasive breast cancer.

BACKGROUND: Recent studies have shown that chemotherapy can cause abnormal glucose and lipid metabolism in breast cancer patients; however, the effects of different chemotherapy regimens on the glucose and lipid profiles in this population remain unclear. METHODS: The clinical data of 141 invasive breast cancer patients who were treated in our center from January 2019 to December 2020 were retrospectively collected. All patients received surgical treatment and postoperative chemotherapy in our center. According to the postoperative chemotherapy regimens, these patients were divided into an observation group (n=100, treated with anthracycline-based regimens) and a control group (n=41, treated with non-anthracycline-based regimens). Blood glucose and lipid profiles were compared between the 2 groups. RESULTS: Compared with the control group, the observation group had a significantly higher radiotherapy rate (74.00% vs. 43.90%, P=0.001) and a significantly higher proportion of patients receiving >6 cycles of chemotherapy (85.00% vs. 4.88%, P=0.000). There were no significant significances in the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) before and after treatment (P>0.05) in both groups. TC and high-density lipoprotein (HDL) were not significantly different between the observation group and control group before chemotherapy (P>0.05). After chemotherapy, fasting blood glucose significantly increased in the observation group (5.31±0.98 vs. 4.96±0.53, P=0.031), while HDL significantly decreased (1.08±0.28 vs. 1.19±0.31, P=0.042). Multivariate logistic regression analysis showed that anthracycline-based chemotherapy was a protective factor for increased fasting blood glucose after chemotherapy in invasive cancer breast patients [P=0.022, odds ratio (OR) =0.227, 95% confidence interval (CI): 0.064-0.808], whereas receiving >6 cycles of chemotherapy was a risk factor for increased fasting blood glucose (P=0.014, OR =4.216, 95% CI: 1.337-13.296). CONCLUSIONS: Anthracyclines have little effect on fasting blood glucose in breast cancer patients; however, the incidence of abnormal blood glucose metabolism is gradually increasing after prolonged anthracycline use. Compared with other chemotherapy drugs, anthracycline-based chemotherapy has no significant impact on blood lipid metabolism.

Effect of postoperative chemotherapy on blood glucose and lipid metabolism in patients with invasive breast cancer.

BACKGROUND: Chemotherapy can lead to abnormal metabolism and affect the quality of life of patients after operation. Here we explore the effect of postoperative chemotherapy on blood glucose and lipid metabolism in patients with invasive breast cancer and thus provide evidence for the prevention and treatment of blood glucose and lipid disorders after surgery. METHODS: From January 2019 to December 2020, data from 141 patients with invasive breast cancer in our hospital were retrospectively collected. The levels of fasting blood glucose and blood lipid profiles [including total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)] were compared before and after chemotherapy. Meanwhile, the metabolic risk factors for abnormal blood glucose and lipid profiles were analyzed. RESULTS: Fasting blood glucose levels significantly increased after treatment (5.21±0.89 vs. 4.87±0.71 mmol/L, P=0.000), as did those of triglyceride (1.81±1.02 vs. 1.26±0.67 mmol/L, P=0.000), while HDL significantly decreased (1.11±0.29 vs. 1.32±0.33 mmol/L, P=0.000). There were no significant differences in the levels of total cholesterol and LDL before and after treatment (P>0.05). Multivariate logistic regression analysis showed that anthracycline-based chemotherapy was a protective factor for elevated fasting blood glucose [P=0.035, 95% CI: 0.248 (0.068-0.908)], whereas receiving >6 cycles of chemotherapy was a risk factor for elevated fasting blood glucose (P=0.026, 95% CI: 4.036 (1.178-13.825)]. CONCLUSIONS: Postoperative chemotherapy can lead to the elevated triglyceride and fasting blood glucose and decreased HDL in patients with breast cancer. Anthracycline-based chemotherapy is a protective factor for the increase of fasting blood glucose, and more than 6 cycles of chemotherapy is a risk factor for the increase of fasting blood glucose.

MR-guided proton therapy: a review and a preview.

BACKGROUND: The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The integration of MRI and PT at the treatment isocenter would offer the opportunity of combining the unparalleled soft-tissue contrast and real-time imaging capabilities of MRI with the most conformal dose distribution and best dose steering capability provided by modern PT. However, hybrid systems for MR-integrated PT (MRiPT) have not been realized so far due to a number of hitherto open technological challenges. In recent years, various research groups have started addressing these challenges and exploring the technical feasibility and clinical potential of MRiPT. The aim of this contribution is to review the different aspects of MRiPT, to report on the status quo and to identify important future research topics. METHODS: Four aspects currently under study and their future directions are discussed: modelling and experimental investigations of electromagnetic interactions between the MRI and PT systems, integration of MRiPT workflows in clinical facilities, proton dose calculation algorithms in magnetic fields, and MRI-only based proton treatment planning approaches. CONCLUSIONS: Although MRiPT is still in its infancy, significant progress on all four aspects has been made, showing promising results that justify further efforts for research and development to be undertaken. First non-clinical research solutions have recently been realized and are being thoroughly characterized. The prospect that first prototype MRiPT systems for clinical use will likely exist within the next 5 to 10 years seems realistic, but requires significant work to be performed by collaborative efforts of research groups and industrial partners.

Reassessment of the Necessity of the Proton Gantry: Analysis of Beam Orientations From 4332 Treatments at the Massachusetts General Hospital Proton Center Over the Past 10 Years.

PURPOSE: To retrospectively analyze the beam approaches used in gantry-based proton treatments, and to reassess the practical advantages of the gantry, compared with beam approaches that are achievable without a gantry, in the context of present-day technology. METHODS AND MATERIALS: We reviewed the proton therapy plans of 4332 patients treated on gantries at our hospital, delivered by the double scattering technique (n=4228) and, more recently, pencil beam scanning (PBS) (n=104). Beam approaches, relative to the patient frame, were analyzed individually to identify cases that could be treated without a gantry. Three treatment configurations were considered, with the patient in lying position, sitting position, or both. The FIXED geometry includes a fixed horizontal portal. The BEND geometry enables a limited vertical inflection of the beam by up to 20°. The MOVE geometry allows for flexibility of the patient head and body setup. RESULTS: The percentage of patients with head and neck tumors that could be treated without a gantry using double scattering was 44% in FIXED, 70% in 20° BEND, and 100% in 90° MOVE. For torso regions, 99% of patients could be treated in 20° BEND. Of 104 PBS treatments, all but 1 could be reproduced with FIXED geometry. The only exception would require a 10° BEND capability. Note here that the PBS treatments were applied to select anatomic sites, including only 2 patients with skull-base tumors. CONCLUSIONS: The majority of practical beam approaches can be realized with gantry-less delivery, aided by limited beam bending and patient movements. Practical limitations of the MOVE geometry, and treatments requiring a combination of lying and sitting positions, may lower the percentage of head and neck patients who could be treated without a gantry. Further investigation into planning, immobilization, and imaging is needed to remove the practical limitations and to facilitate proton treatment without a gantry.

A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems.

PURPOSE: To construct a robotic SPECT system and to demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch, as a step toward onboard functional and molecular imaging in radiation therapy. METHODS: A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with a phantom (PET CT Phantom(TM)), which includes five spheres of 10, 13, 17, 22, and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT projections were acquired either with a parallel-hole collimator or a single-pinhole collimator, both without background in the phantom and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180° and 228°, respectively. The pinhole detector viewed an off-centered spherical common volume which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole system was centered at the phantom which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the phantom and flat-top table while avoiding collision and maintaining the closest possible proximity to the common volume. The robot base and tool coordinates were used for image reconstruction. RESULTS: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector radius of rotation. Without background, all five spheres were visible in the reconstructed parallel-hole image, while four spheres, all except the smallest one, were visible in the reconstructed pinhole image. With background, three spheres of 17, 22, and 28 mm diameters were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters) were readily observed in the pinhole region-of-interest imaging. CONCLUSIONS: Onboard SPECT could be achieved by a robot maneuvering a SPECT detector about patients in position for radiation therapy on a flat-top couch. The robot inherent coordinate frames could be an effective means to estimate detector pose for use in SPECT image reconstruction.

Onboard functional and molecular imaging: a design investigation for robotic multipinhole SPECT.

PURPOSE: Onboard imaging-currently performed primarily by x-ray transmission modalities-is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. METHODS: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. RESULTS: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. CONCLUSIONS: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min scan times.

A line-source method for aligning on-board and other pinhole SPECT systems.

PURPOSE: In order to achieve functional and molecular imaging as patients are in position for radiation therapy, a robotic multipinhole SPECT system is being developed. Alignment of the SPECT system-to the linear accelerator (LINAC) coordinate frame and to the coordinate frames of other on-board imaging systems such as cone-beam CT (CBCT)-is essential for target localization and image reconstruction. An alignment method that utilizes line sources and one pinhole projection is proposed and investigated to achieve this goal. Potentially, this method could also be applied to the calibration of the other pinhole SPECT systems. METHODS: An alignment model consisting of multiple alignment parameters was developed which maps line sources in three-dimensional (3D) space to their two-dimensional (2D) projections on the SPECT detector. In a computer-simulation study, 3D coordinates of line-sources were defined in a reference room coordinate frame, such as the LINAC coordinate frame. Corresponding 2D line-source projections were generated by computer simulation that included SPECT blurring and noise effects. The Radon transform was utilized to detect angles (α) and offsets (ρ) of the line-source projections. Alignment parameters were then estimated by a nonlinear least squares method, based on the α and ρ values and the alignment model. Alignment performance was evaluated as a function of number of line sources, Radon transform accuracy, finite line-source width, intrinsic camera resolution, Poisson noise, and acquisition geometry. Experimental evaluations were performed using a physical line-source phantom and a pinhole-collimated gamma camera attached to a robot. RESULTS: In computer-simulation studies, when there was no error in determining angles (α) and offsets (ρ) of the measured projections, six alignment parameters (three translational and three rotational) were estimated perfectly using three line sources. When angles (α) and offsets (ρ) were provided by the Radon transform, estimation accuracy was reduced. The estimation error was associated with rounding errors of Radon transform, finite line-source width, Poisson noise, number of line sources, intrinsic camera resolution, and detector acquisition geometry. Statistically, the estimation accuracy was significantly improved by using four line sources rather than three and by thinner line-source projections (obtained by better intrinsic detector resolution). With five line sources, median errors were 0.2 mm for the detector translations, 0.7 mm for the detector radius of rotation, and less than 0.5° for detector rotation, tilt, and twist. In experimental evaluations, average errors relative to a different, independent registration technique were about 1.8 mm for detector translations, 1.1 mm for the detector radius of rotation (ROR), 0.5° and 0.4° for detector rotation and tilt, respectively, and 1.2° for detector twist. CONCLUSIONS: Alignment parameters can be estimated using one pinhole projection of line sources. Alignment errors are largely associated with limited accuracy of the Radon transform in determining angles (α) and offsets (ρ) of the line-source projections. This alignment method may be important for multipinhole SPECT, where relative pinhole alignment may vary during rotation. For pinhole and multipinhole SPECT imaging on-board radiation therapy machines, the method could provide alignment of SPECT coordinates with those of CBCT and the LINAC.