Artificial intelligence strategy integrating morphologic and architectural biomarkers provides robust diagnostic accuracy for disease progression in chronic lymphocytic leukemia.

Artificial intelligence-based tools designed to assist in the diagnosis of lymphoid neoplasms remain limited. The development of such tools can add value as a diagnostic aid in the evaluation of tissue samples involved by lymphoma. A common diagnostic question is the determination of chronic lymphocytic leukemia (CLL) progression to accelerated CLL (aCLL) or transformation to diffuse large B-cell lymphoma (Richter transformation; RT) in patients who develop progressive disease. The morphologic assessment of CLL, aCLL, and RT can be diagnostically challenging. Using established diagnostic criteria of CLL progression/transformation, we designed four artificial intelligence-constructed biomarkers based on cytologic (nuclear size and nuclear intensity) and architectural (cellular density and cell to nearest-neighbor distance) features. We analyzed the predictive value of implementing these biomarkers individually and then in an iterative sequential manner to distinguish tissue samples with CLL, aCLL, and RT. Our model, based on these four morphologic biomarker attributes, achieved a robust analytic accuracy. This study suggests that biomarkers identified using artificial intelligence-based tools can be used to assist in the diagnostic evaluation of tissue samples from patients with CLL who develop aggressive disease features. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Digitally enabled hemovigilance allows real time response to transfusion reactions.

BACKGROUND: Transfusion carries a risk of transfusion reaction that is often underdiagnosed due to reliance on passive reporting. The study investigated the utility of digital methods to identify potential transfusion reactions, thus allowing real-time intervention for affected patients. METHOD: The hemovigilance unit monitored 3856 patients receiving 43,515 transfusions under the hemovigilance program. Retrospective comparison data included 298,498 transfusions. Transfusion medicine physicians designed and validated algorithms in the electronic health record that analyze discrete data, such as vital sign changes, to assign a risk score during each transfusion. Dedicated hemovigilance nurses remotely monitor all patients and perform real-time chart reviews prioritized by risk score. When a reaction is suspected, a hemovigilance trained licensed clinician responds to manage the patient and ensure data collection. Board-certified transfusion medicine physicians reviewed data and classified transfusion reactions under various categories according to the Centers for Disease Control hemovigilance definitions. RESULTS: Transfusion medicine physicians diagnosed 564 transfusion reactions (1.3% of transfusions)-a 524% increase compared to the previous passive reporting. The rapid response provider reached the bedside on average at 12.4 min demonstrating logistic feasibility. While febrile reactions were most diagnosed, recognition of transfusion-associated circulatory overload demonstrated the greatest relative increase. Auditing and education programs further enhanced transfusion reaction awareness. DISCUSSION: The model of digitally-enabled expert real-time review of clinical data that prompts rapid response improved recognition of transfusion reactions. This approach could be applied to other patient deterioration events such as early identification of sepsis.

Assessment of a liposomal CT/optical contrast agent for image-guided head and neck surgery.

This study evaluates a long-acting liposomal fluorescence / CT dual-modality contrast agent (CF800) in head and neck cancer to enhance intraoperative tumor demarcation with fluorescence imaging and cone-beam computed tomography (CBCT). CF800 was administered to 12 buccal cancer-bearing rabbits. Imaging was acquired at regular time points to quantify time-dependent contrast enhancement. Surgery was performed 5-7 days after, with intraoperative near-infrared fluorescence endoscopy and CBCT, followed by histological and ex-vivo fluorescence assessment. Tumor enhancement on CT was significant at 24, 96 and 120 hours. Volumetric analysis of tumor segmentation showed high correlation between CBCT and micro-CT. Fluorescence signal was apparent in both ex-vivo and in-vivo imaging. Histological correlation showed [100%] specificity for primary tumor. Sensitivity and specificity of CF800 in detecting nodal involvement require further investigation.CF800 is long acting and has dual function for CT and fluorescence contrast, making it an excellent candidate for image-guided surgery.

Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact.

BACKGROUND: Radiotherapy is standard of care for cervical cancer, but major global gaps in access exist, particularly in low-income and middle-income countries. We modelled the health and economic benefits of a 20-year radiotherapy scale-up to estimate the long-term demand for treatment in the context of human papillomavirus (HPV) vaccination. METHODS: We applied the Global Task Force on Radiotherapy for Cancer Control investment framework to model the health and economic benefits of scaling up external-beam radiotherapy and brachytherapy for cervical cancer in upper-middle-income, lower-middle-income, and low-income countries between 2015 and 2035. We estimated the unique costs of external-beam radiotherapy and brachytherapy and included a specific valuation of women's caregiving contributions. Model outcomes life-years gained and the human capital and full income net present value of investment. We estimated the effects of stage at diagnosis, radiotherapy delivery system, and simultaneous HPV vaccination (75% coverage) up to a time horizon set at 2072. FINDINGS: For the period from 2015 to 2035, we estimated that 9·4 million women in low-income and middle-income countries required treatment with external-beam radiotherapy, of which 7·0 million also required treatment with brachytherapy. Incremental scale-up of radiotherapy in these countries from 2015 to meet optimal radiotherapy demand by 2035 yielded 11·4 million life-years gained, $59·3 billion in human capital net present value (-$1·5 billion in low-income, $19·9 billion in lower-middle-income, and $40·9 billion in upper-middle-income countries), and $151·5 billion in full income net present value ($1·5 billion in low-income countries, $53·6 billion in lower-middle-income countries, and $96·4 billion in upper-middle-income countries). Benefits increased with advanced stage of cervical cancer and more efficient scale up of radiotherapy. Bivalent HPV vaccination of 12-year-old girls resulted in a 3·9% reduction in incident cases from 2015-2035. By 2072, when the first vaccinated cohort of girls reaches 70 years of age, vaccination yielded a 22·9% reduction in cervical cancer incidence, with 38·4 million requiring external-beam radiotherapy and 28·8 million requiring brachytherapy. INTERPRETATION: Effective cervical cancer control requires a comprehensive strategy. Even with HPV vaccination, radiotherapy treatment scale-up remains essential and produces large health benefits and a strong return on investment to countries at different levels of development. FUNDING: None.

Costs, affordability, and feasibility of an essential package of cancer control interventions in low-income and middle-income countries: key messages from Disease Control Priorities, 3rd edition.

Investments in cancer control--prevention, detection, diagnosis, surgery, other treatment, and palliative care--are increasingly needed in low-income and particularly in middle-income countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities, 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades.

A novel field emission microscopy method to study field emission characteristics of freestanding carbon nanotube arrays.

Field emission (FE) uniformity and the mechanism of emitter failure of freestanding carbon nanotube (CNT) arrays have not been well studied due to the difficulty of observing and quantifying FE performance of each emitter in CNT arrays. Herein a field emission microscopy (FEM) method based on poly(methyl methacrylate) (PMMA) thin film is proposed to study the FE uniformity and CNT emitter failure of freestanding CNT arrays. FE uniformity of freestanding CNT arrays and different levels of FE current contributions from each emitter in the arrays are recorded and visualized. FEM patterns on the PMMA thin film contain the details of the CNT emitter tip shape and whether multiple CNT emitters occur at an emission site. Observation of real-time FE performance and the CNT emitter failure process in freestanding CNT arrays are successfully achieved using a microscopic camera. High emission currents through CNT emitters causes Joule heating and light emission followed by an explosion of the CNTs. The proposed approach is capable of resolving the major challenge of building the relationship between FE performance and CNT morphologies, which can significantly facilitate the study of FE non-uniformity, the emitter failure mechanism and the development of stable and reliable FE devices in practical applications.

Only walking matters-assessment following lumbar stenosis decompression.

PURPOSE: Multiple outcome measures exist to evaluate the outcomes of spinal decompression surgery; however, these tend to be complex and are difficult to express to the patient pre-operatively to accurately guide their expectations. We present outcomes, in terms of walking distance measurement, of a prospective single surgeon series of 76 consecutive patients with spinal stenosis. METHODS: 76 patients (mean age 68.8 years; 48-91 years) had decompression surgery using spinous process osteotomy. Accurate measurement of walking distance was used as an outcome measure, and factors that affect it were evaluated. Walking distance was measured pre-operatively, post-operatively and at 3 months follow-up using a measuring wheel. The minimum follow-up was 5 years. RESULTS: The mean distances walked were 78.1, 419.9 and 1285 m, respectively. Pre-operative disc height (p = 0.023) and male gender (p = 0.039) predicted a significant improvement in walking distance, while age (p = 0.23), ASA grade (p = 0.39) and the number of levels operated on (p = 0.89) did not significantly affect the increase in walking distance. 12 patients experienced post-operative complications (15.8%), and at last clinical follow-up (6.3 years, 5.1-6.9 years) 27 patients (35.5%) had residual leg symptoms and 8 had undergone further revision procedures (10.5%). CONCLUSION: This study demonstrates that walking distance is an accurate and accessible method of determining surgical outcomes.

The outcome of decompression alone for lumbar spinal stenosis with degenerative spondylolisthesis.

PURPOSE: Lumbar spinal stenosis in the presence of degenerative spondylolisthesis is generally treated by means of surgery. The role of lumbar decompression without fusion is not clear. Therefore, the aim of this study was to assess whether patients who undergo decompression alone have a favourable outcome without the need for a subsequent fusion. METHODS: This is a prospective cohort study with single blinding of 83 consecutive patients with lumbar stenosis and degenerative spondylolisthesis treated by decompression, without fusion, using a spinous process osteotomy. Blinded observers collected pre- and post-operative Oswestry Disability Index (ODI), EuroQol Five Dimensions (EQ-5D), and visual analogue scale (VAS) for back and leg pain scores prospectively. Failures for this study were those patients who required a subsequent lumbar fusion procedure at the decompressed levels. Statistical analysis was performed using paired t test and Mann-Whitney test. RESULTS: There were 36 males and 47 females with a mean age of 66 years (range 35-82). The mean follow-up was 36 months (range 19-48 months). The mean pre-operative ODI, EQ-5D, and VAS scores were 52 [standard deviation (SD) 18], 0.25 (SD 0.30), and 61 (SD 22), respectively. All mean scores improved post-operatively to 38 (SD 23), 0.54 (SD 0.34) and 36 (SD 27), respectively. There was a statistically significant improvement in all scores (p ≤ 0.0001). Nine patients (11 %) required a subsequent fusion procedure and five patients (6 %) required revision decompression surgery alone. CONCLUSION: Our study's results show that a lumbar decompression procedure without arthrodesis in a consecutive cohort of patients with lumbar spinal stenosis with degenerative spondylolisthesis had a significant post-operative improvement in ODI, EQ-5D, and VAS. The rate of post-operative instability and subsequent fusion is not high. Only one in 10 patients in this group ended up needing a subsequent fusion at a mean follow-up of 36 months, indicating that fusion is not always necessary in these patients.

Expanding global access to radiotherapy.

Radiotherapy is a critical and inseparable component of comprehensive cancer treatment and care. For many of the most common cancers in low-income and middle-income countries, radiotherapy is essential for effective treatment. In high-income countries, radiotherapy is used in more than half of all cases of cancer to cure localised disease, palliate symptoms, and control disease in incurable cancers. Yet, in planning and building treatment capacity for cancer, radiotherapy is frequently the last resource to be considered. Consequently, worldwide access to radiotherapy is unacceptably low. We present a new body of evidence that quantifies the worldwide coverage of radiotherapy services by country. We show the shortfall in access to radiotherapy by country and globally for 2015-35 based on current and projected need, and show substantial health and economic benefits to investing in radiotherapy. The cost of scaling up radiotherapy in the nominal model in 2015-35 is US$26·6 billion in low-income countries, $62·6 billion in lower-middle-income countries, and $94·8 billion in upper-middle-income countries, which amounts to $184·0 billion across all low-income and middle-income countries. In the efficiency model the costs were lower: $14·1 billion in low-income, $33·3 billion in lower-middle-income, and $49·4 billion in upper-middle-income countries-a total of $96·8 billion. Scale-up of radiotherapy capacity in 2015-35 from current levels could lead to saving of 26·9 million life-years in low-income and middle-income countries over the lifetime of the patients who received treatment. The economic benefits of investment in radiotherapy are very substantial. Using the nominal cost model could produce a net benefit of $278·1 billion in 2015-35 ($265·2 million in low-income countries, $38·5 billion in lower-middle-income countries, and $239·3 billion in upper-middle-income countries). Investment in the efficiency model would produce in the same period an even greater total benefit of $365·4 billion ($12·8 billion in low-income countries, $67·7 billion in lower-middle-income countries, and $284·7 billion in upper-middle-income countries). The returns, by the human-capital approach, are projected to be less with the nominal cost model, amounting to $16·9 billion in 2015-35 (-$14·9 billion in low-income countries; -$18·7 billion in lower-middle-income countries, and $50·5 billion in upper-middle-income countries). The returns with the efficiency model were projected to be greater, however, amounting to $104·2 billion (-$2·4 billion in low-income countries, $10·7 billion in lower-middle-income countries, and $95·9 billion in upper-middle-income countries). Our results provide compelling evidence that investment in radiotherapy not only enables treatment of large numbers of cancer cases to save lives, but also brings positive economic benefits.

Contrast Agent Mass Spectrometry Imaging Reveals Tumor Heterogeneity.

Mapping intratumoral heterogeneity such as vasculature and margins is important during intraoperative applications. Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated potential for intraoperative tumor imaging using validated MS profiles. The clinical translation of DESI-MS into a universal label-free imaging technique thus requires access to MS profiles characteristic to tumors and healthy tissues. Here, we developed contrast agent mass spectrometry imaging (CA-MSI) that utilizes a magnetic resonance imaging (MRI) contrast agent targeted to disease sites, as a label, to reveal tumor heterogeneity in the absence of known MS profiles. Human breast cancer tumors grown in mice were subjected to CA-MSI using Gadoteridol revealing tumor margins and vasculature from the localization of [Gadoteridol+K](+) and [Gadoteridol+Na](+) adducts, respectively. The localization of the [Gadoteridol+K](+) adduct as revealed through DESI-MS complements the in vivo MRI results. DESI-MS imaging is therefore possible for tumors for which no characteristic MS profiles are established. Further DESI-MS imaging of the flux of the contrast agent through mouse kidneys was performed indicating secretion of the intact label.

Ambient Mass Spectrometry Imaging with Picosecond Infrared Laser Ablation Electrospray Ionization (PIR-LAESI).

A picosecond infrared laser (PIRL) is capable of cutting through biological tissues in the absence of significant thermal damage. As such, PIRL is a standalone surgical scalpel with the added bonus of minimal postoperative scar tissue formation. In this work, a tandem of PIRL ablation with electrospray ionization (PIR-LAESI) mass spectrometry is demonstrated and characterized for tissue molecular imaging, with a limit of detection in the range of 100 nM for reserpine or better than 5 nM for verapamil in aqueous solution. We characterized PIRL crater size using agar films containing Rhodamine. PIR-LAESI offers a 20-30 µm vertical resolution (∼3 µm removal per pulse) and a lateral resolution of ∼100 µm. We were able to detect 25 fmol of Rhodamine in agar ablation experiments. PIR-LAESI was used to map the distribution of endogenous methoxykaempferol glucoronide in zebra plant (Aphelandra squarrosa) leaves producing a localization map that is corroborated by the literature. PIR-LAESI was further used to image the distribution inside mouse kidneys of gadoteridol, an exogenous magnetic resonance contrast agent intravenously injected. Parallel mass spectrometry imaging (MSI) using desorption electrospray ionization (DESI) and matrix assisted laser desorption ionization (MALDI) were performed to corroborate PIR-LAESI images of the exogenous agent. We further show that PIR-LAESI is capable of desorption ionization of proteins as well as phospholipids. This comparative study illustrates that PIR-LAESI is an ion source for ambient mass spectrometry applications. As such, a future PIRL scalpel combined with secondary ionization such as ESI and mass spectrometry has the potential to provide molecular feedback to guide PIRL surgery.

MR-guided prostate biopsy for planning of focal salvage after radiation therapy.

PURPOSE: To determine if the integration of diagnostic magnetic resonance (MR) imaging and MR-guided biopsy would improve target delineation for focal salvage therapy in men with prostate cancer. MATERIALS AND METHODS: Between September 2008 and March 2011, 30 men with biochemical failure after radiation therapy for prostate cancer provided written informed consent and were enrolled in a prospective clinical trial approved by the institutional research ethics board. An integrated diagnostic MR imaging and interventional biopsy procedure was performed with a 1.5-T MR imager by using a prototype table and stereotactic transperineal template. Multiparametric MR imaging (T2-weighted, dynamic contrast material-enhanced, and diffusion-weighted sequences) was followed by targeted biopsy of suspicious regions and systematic sextant sampling. Biopsy needle locations were imaged and registered to diagnostic images. Two observers blinded to clinical data and the results of prior imaging studies delineated tumor boundaries. Area under the receiver operating characteristic curve (Az) was calculated based on generalized linear models by using biopsy as the reference standard to distinguish benign from malignant lesions. RESULTS: Twenty-eight patients were analyzed. Most patients (n = 22) had local recurrence, with 82% (18 of 22) having unifocal disease. When multiparametric volumes from two observers were combined, it increased the apparent overall tumor volume by 30%; however, volumes remained small (mean, 2.9 mL; range, 0.5-8.3 mL). Tumor target boundaries differed between T2-weighted, dynamic contrast-enhanced, and diffusion-weighted sequences (mean Dice coefficient, 0.13-0.35). Diagnostic accuracy in the identification of tumors improved with a multiparametric approach versus a strictly T2-weighted or dynamic contrast-enhanced approach through an improvement in sensitivity (observer 1, 0.65 vs 0.35 and 0.44, respectively; observer 2, 0.82 vs 0.64 and 0.53, respectively; P < .05) and improved further with a 5-mm expansion margin (Az = 0.85 vs 0.91 for observer 2). After excluding three patients with fewer than six informative biopsy cores and six patients with inadequately stained margins, MR-guided biopsy enabled more accurate delineation of the tumor target volume be means of exclusion of false-positive results in 26% (five of 19 patients), false-negative results in 11% (two of 19 patients) and by guiding extension of tumor boundaries in 16% (three of 19 patients). CONCLUSION: The integration of guided biopsy with diagnostic MR imaging is feasible and alters delineation of the tumor target boundary in a substantial proportion of patients considering focal salvage.

A gradient-loadable (64)Cu-chelator for quantifying tumor deposition kinetics of nanoliposomal therapeutics by positron emission tomography.

Effective drug delivery to tumors is a barrier to treatment with nanomedicines. Non-invasively tracking liposome biodistribution and tumor deposition in patients may provide insight into identifying patients that are well-suited for liposomal therapies. We describe a novel gradient-loadable chelator, 4-DEAP-ATSC, for incorporating (64)Cu into liposomal therapeutics for positron emission tomographic (PET). (64)Cu chelated to 4-DEAP-ATSC (>94%) was loaded into PEGylated liposomal doxorubicin (PLD) and HER2-targeted PLD (MM-302) with efficiencies >90%. (64)Cu-MM-302 was stable in human plasma for at least 48h. PET/CT imaging of xenografts injected with (64)Cu-MM-302 revealed biodistribution profiles that were quantitatively consistent with tissue-based analysis, and tumor (64)Cu positively correlated with liposomal drug deposition. This loading technique transforms liposomal therapeutics into theranostics and is currently being applied in a clinical trial (NCT01304797) to non-invasively quantify MM-302 tumor deposition, and evaluate its potential as a prognostic tool for predicting treatment outcome of nanomedicines.

Electron transfer-based combination therapy of cisplatin with tetramethyl-p-phenylenediamine for ovarian, cervical, and lung cancers.

The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug. Here, we show that the combination of cisplatin with an exemplary biological electron donor, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), may overcome the resistance of cancer cells to cisplatin. Our steady-state absorption and fluorescence spectroscopic measurements confirm the effective dissociative electron-transfer reaction between TMPD and cisplatin. More significantly, we found that the combination of 100 µM TMPD with cisplatin enhances double-strand breaks of plasmid DNA by a factor of approximately 3.5 and dramatically reduces the viability of cisplatin-sensitive human cervical (HeLa) cancer cells and highly cisplatin-resistant human ovarian (NIH:OVCAR-3) and lung (A549) cancer cells. Furthermore, this combination enhances apoptosis and DNA fragmentation by factors of 2-5 compared with cisplatin alone. These results demonstrate that this combination treatment not only results in a strong synergetic effect, but also makes resistant cancer cells sensitive to cisplatin. Because cisplatin is the cornerstone agent for the treatment of a variety of human cancers (including testicular, ovarian, cervical, bladder, head/neck, and lung cancers), our results show both the potential to improve platinum-based chemotherapy of various human cancers and the promise of femtomedicine as an emerging frontier in advancing cancer therapy.

Direct observation of ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage.

Both water and electron-transfer reactions play important roles in chemistry, physics, biology, and the environment. Oxidative DNA damage is a well-known mechanism, whereas the relative role of reductive DNA damage is unknown. The prehydrated electron (e(pre)-), a novel species of electrons in water, is a fascinating species due to its fundamental importance in chemistry, biology, and the environment. e(pre)- is an ideal agent to observe reductive DNA damage. Here, we report both the first in situ femtosecond time-resolved laser spectroscopy measurements of ultrafast-electron-transfer (UET) reactions of e(pre)- with various scavengers (KNO(3), isopropanol, and dimethyl sulfoxide) and the first gel electrophoresis measurements of DNA strand breaks induced by e(pre)- and OH(•) radicals co-produced by two-UV-photon photolysis of water. We strikingly found that the yield of reductive DNA strand breaks induced by each e(pre)- is twice the yield of oxidative DNA strand breaks induced by each OH(•) radical. Our results not only unravel the long-standing mystery about the relative role of radicals in inducing DNA damage under ionizing radiation, but also challenge the conventional notion that oxidative damage is the main pathway for DNA damage. The results also show the potential of femtomedicine as a new transdisciplinary frontier and the broad significance of UET reactions of e(pre)- in many processes in chemistry, physics, biology, and the environment.

Proof-of-concept for a thin conical X-ray target optimized for intensity and directionality for use in a carbon nanotube-based compact X-ray tube.

BACKGROUND: Carbon nanotube-based cold cathode technology has revolutionized the miniaturization of X-ray tubes. However, current applications of these devices required optimization for large, uniform fields with low intensity. PURPOSE: This work investigated the feasibility and radiological characteristics of a novel conical X-ray target optimized for high intensity and high directionality to be used in a compact X-ray tube. METHODS: The proposed device uses an ultrathin, conical tungsten-diamond target that exhibits significant heat loading while maintaining a small focal spot size and promoting forward-directedness of the X-ray field through preferential attenuation of oblique-angled photons. The electrostatic and thermal properties of the theoretical tube were calculated and analyzed using COMSOL Multiphysics software. The production, transport, and calculation of radiological properties associated with the resultant X-ray field were performed using the Geant4 toolkit via its wrapper, TOPAS. RESULTS: Heat transfer analysis of this X-ray tube demonstrated the feasibility of a 200-kV electron beam bombarding the proposed target at a maximum current of 100 mA using a 1-ms symmetric duty cycle. The cathode of the X-ray tube was designed to be segmented into nine switchable electrical segments for modulation of the focal spot size from 0.4- to 10.8-mm. After importing the COMSOL-derived electron beam into TOPAS for X-ray production simulations, radiological analysis of the resultant field demonstrated high levels of intrinsic beam collimation while maintaining high intensity. A maximum dose rate of 17,887 cGy/min was calculated for 1-mm depth in water at 7-cm distance. CONCLUSIONS: The proposed X-ray tube design can create highly directional X-ray fields with superior fluence compared to that of current commercial X-ray tubes of comparable size.

The Future of MR-Guided Radiation Therapy.

Magnetic resonance image guided radiation therapy (MRIgRT) is a relatively new technology that has already shown outcomes benefits but that has not yet reached its clinical potential. The improved soft-tissue contrast provided with MR, coupled with the immediacy of image acquisition with respect to the treatment, enables expansion of on-table adaptive protocols, currently at a cost of increased treatment complexity, use of human resources, and longer treatment slot times, which translate to decreased throughput. Many approaches are being investigated to meet these challenges, including the development of artificial intelligence (AI) algorithms to accelerate and automate much of the workflow and improved technology that parallelizes workflow tasks, as well as improvements in image acquisition speed and quality. This article summarizes limitations of current available integrated MRIgRT systems and gives an outlook about scientific developments to further expand the use of MRIgRT.