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Stereotactic body radiation therapy (SBRT) is a recognized treatment for low- and intermediate-risk prostate cancer, with 36.25 Gy in 5 fractions the most commonly used regimen. We explored the preliminary efficacy, patient recorded toxicity, and decision regret in intermediate- and high-risk prostate cancer receiving SBRT with prostate-specific membrane antigen (PSMA)/magnetic resonance imaging (MRI) guided focal gross tumor volume boost to 45 Gy.Between July 2015 and June 2019, 120 patients received SBRT across 2 institutions with a uniform protocol. All patients had fiducial markers and hydrogel, MRI and PSMA positron emission tomography (PET) scan. All patients received a questionnaire asking the degree of urinary, bowel, and sexual bother experienced at set time points, including questions about treatment choice and decision regret.One hundred twelve of 120 patients consented. Their median age was 72 years and median follow-up was 2.3 years. As per National Comprehensive Cancer Network guidelines, 78% had intermediate risk and 20% high risk. Androgen deprivation was combined with radiation in 6 patients. Most patients (74%) reported that receiving SBRT significantly influenced their choice of treatment. Five men (4%) expressed "quite a lot" (n = 4) or "very much" regret (n = 1) regarding their choice of treatment, while 89% expressed "no regret." Similar to pretreatment levels, "quite a lot" or "very much" urinary or bowel bother was expressed in 8% and 6% of patients, respectively. Two patients experienced nadir +2 biochemical failure, both found to have bone metastases. A third patient underwent PSMA PET at nadir +1.7 and had disease at the penile bulb, which was out of field. Three year estimated freedom from biochemical failure was 99% for intermediate and 85% for high-risk groups.We have demonstrated promising efficacy and low toxicity with PSMA/MRI-guided SBRT focal boost. Less than 5% of patients expressed significant decision regret for their choice of treatment.

Magnetic resonance guided radiotherapy (MRgRT), enabled by the clinical introduction of the integrated MRI and linear accelerator (MR-LINAC), is a novel technique for prostate cancer (PCa) treatment, promising to further improve clinical outcome and reduce toxicity. The role of prostate MRI has been greatly expanded from the traditional PCa diagnosis to also PCa screening, treatment and surveillance. Diagnostic prostate MRI has been relatively familiar in the community, particularly with the development of Prostate Imaging - Reporting and Data System (PI-RADS). But, on the other hand, the use of MRI in the emerging clinical practice of PCa MRgRT, which is substantially different from that in PCa diagnosis, has been so far sparsely presented in the medical literature. This review attempts to give a comprehensive overview of MRI acquisition techniques currently used in the clinical workflows of PCa MRgRT, from treatment planning to online treatment guidance, in order to promote MRI practice and research for PCa MRgRT. In particular, the major differences in the MRI acquisition of PCa MRgRT from that of diagnostic prostate MRI are demonstrated and explained. Limitations in the current MRI acquisition for PCa MRgRT are analyzed. The future developments of MRI in the PCa MRgRT are also discussed.

Highlights • Thermoplastic masks are widely used in clinical routine on conventional LINACs. • Patient setup is more challenging on MR-LINAC systems. • lOn the MRIdian system, there is no dedicated holder for the anterior receiver coil. • We evaluated the suitability of a customised coil support system for MRgRT. • (MR) image uniformity measurements demonstrated improved image uniformity. • Fixed distancing between the receiver coils and the patient is possible. • This coil support system represents a solution for stable anterior coil placement., Magnetic resonance imaging (MR)-guided online adaptive radiotherapy is a promising technique in the field of radiation oncology providing excellent visualisation of soft-tissues, and allowing for online plan adaptation and tumour tracking. In order to facilitate the accurate dose delivery to the target volume while sparing healthy surrounding normal tissue in the brain or head-and-neck (H&N) region, precise patient immobilisation with good image quality is pertinent. Herein, we present a customised thermoplastic mask holder with an integrated anterior MR receiver coil support system for MR-guided online adaptive radiotherapy in the brain and head-and-neck region. The approved medical product was developed by Innovative Technologie Voelp (IT-V), Innsbruck, Austria. MR image uniformity measurements demonstrated improved image uniformity at the expense of decreased signal-to-noise ratio due to a more defined and larger distance between the anterior receiver coil and the phantom or patient. This integrated coil support system represents a practical solution facilitating stable and reproducible anterior coil placement while maintaining the thermoplastic mask holder functionality, a widely established immobilisation technique.

Background and purpose: Atrial fibrillation (AF) cardiac radioablation (CR) challenges radiotherapy tracking: multiple small targets close to organs-at-risk undergo rapid differential cardiac contraction and respiratory motion. MR-guidance offers a real-time target tracking solution. This work develops and investigates MRI-guided tracking of AF CR targets with cardiac-induced motion. Materials and methods: A direct tracking method (Trackingdirect) and two indirect tracking methods leveraging population-based surrogacy relationships with the left atria (Trackingindirect_LA) or other target (Trackingindirect_target) were developed. Tracking performance was evaluated using transverse ECG-gated breathhold MRI images from 15 healthy and 10 AF participants. Geometric and volumetric tracking errors were calculated, defined as the difference between the ground-truth and tracked target centroids and volumes respectively. Transverse, breath-hold, noncardiac-gated cine images were acquired at 4 Hz in 5 healthy and 5 AF participants to qualitatively characterize tracking performance on images more comparable to MRILinac acquisitions. Results: The average 3D geometric tracking errors for Trackingdirect, Trackingindirect_LA and Trackingindirect_target respectively were 1.7 ± 1.2 mm, 1.6 ± 1.1 mm and 1.9 ± 1.3 mm in healthy participants and 1.7 ± 1.3 mm, 1.5 ± 1.0 mm and 1.7 ± 1.2 mm in AF participants. For Trackingdirect, 88% of analyzed images had 3D geometric tracking errors

PURPOSE To design and manufacture a pelvis phantom for magnetic resonance (MR)-guided prostate interventions, such as MRGB (MR-guided biopsy) or brachytherapy seed placement. METHODS The phantom was designed to mimic the human pelvis incorporating bones, bladder, prostate with four lesions, urethra, arteries, veins, and six lymph nodes embedded in ballistic gelatin. A hollow rectum enables transrectal access to the prostate. To demonstrate the feasibility of the phantom for minimal invasive MRI-guided interventions, a targeted inbore MRGB was performed. The needle probe was rectally inserted and guided using an MRI-compatible remote controlled manipulator (RCM). RESULTS The presented pelvis phantom has realistic imaging properties for MR imaging (MRI), computed tomography (CT) and ultrasound (US). In the targeted inbore MRGB, a prostate lesion was successfully hit with an accuracy of 3.5 mm. The experiment demonstrates that the limited size of the rectum represents a realistic impairment for needle placements. CONCLUSION The phantom provides a valuable platform for evaluating the performance of MRGB systems. Interventionalists can use the phantom to learn how to deal with challenging situations, without risking harm to patients.

Contains fulltext : 238625.pdf (Publisher’s version ) (Open Access) Microbrachytherapy with radioactive holmium-166 ((166)Ho) microspheres (MS) has the potential to be an effective treatment method for brain malignancies. Direct intratumoural delivery of (166)Ho-MS and dose coverage of the whole tumour are crucial requirements. However, currently no dedicated instruments for controlled intratumoural delivery exist. This study presents an administration device that facilitates this novel magnetic resonance imaging (MRI) -guided intervention. The bioceramic alumina oxide cannula creates a straight channel for a superelastic nitinol precurved stylet to control spatial deposition of Ho-MS. End-point accuracy of the stylet was measured during insertions in phantoms. Imaging tests were performed in a 3 Tesla MRI-scanner to quantify instrument-induced artefacts. Additionally, the feasibility of non-radioactive holmium-165 ((165)Ho)-MS delivery with the administration device was evaluated in a brain tumour simulant. Absolute stylet tip error was 0.88 +/- 0.61 mm, instrument distortion in MRI depended on needle material and orientation and dose delivery of (165)Ho-MS in a brain tumour phantom was possible. This study shows that the administration device can accurately place the stylet for injection of Ho-MS and that visualization can be performed with MRI.

The current standard treatment for locally advanced or metastatic colorectal cancer often includes radiotherapy delivered under computed tomography (CT)–based image guidance. Magnetic resonance–guided radiotherapy (MRgRT) offers a substantial improvement in target and adjacent organ visualization and allows for real-time imaging throughout treatment to ensure target accuracy with each fraction. However, this technology is in its relative infancy, with many open questions regarding how to maximize the potential of this new treatment modality. We review the literature and share our institutional experience to highlight the strengths and limitations of MRgRT for treatment of colorectal cancer. MRgRT is safe and effective in both the locally advanced and metastatic settings. Dose can be safely escalated in locally advanced cases, potentially improving rates of pathologic complete response. Functional imaging offers insight into treatment response dynamics, opening the possibility for nonoperative management of select cases. Liver metastases can be treated to ablative doses with high rates of local control. MRgRT has the potential to shift the paradigm of treatment for locally advanced and metastatic colorectal cancer. Improved target accuracy and real-time gating allows for dose prescriptions beyond what has been achievable with CT-based imaging, allowing for higher rates of tumor control with no significant increase in toxicity. Future work will focus on optimal dose fractionation schemes and functional radiographic assessment of tumor response.

Introduction: There is still a lack of availability of high-quality multiparametric magnetic resonance imaging (mpMRI) interpreted by experienced uro-radiologists to rule out clinically significant PC (csPC). Consequently, we developed a new imaging method based on computed tomographic ultrasound (US) supported by artificial neural network analysis (ANNA). Methods: Two hundred and two consecutive patients with visible mpMRI lesions were scanned and recorded by robotic CT-US during mpMRI-TRUS biopsy. Only significant index lesions (ISUP ≥2) verified by whole-mount pathology were retrospectively analyzed. Their visibility was reevaluated by 2 blinded investigators by grayscale US and ANNA. Results: In the cohort, csPC was detected in 105 cases (52%) by mpMRI-TRUS biopsy. Whole-mount histology was available in 44 cases (36%). In this subgroup, mean PSA level was 8.6 ng/mL, mean prostate volume was 33 cm3, and mean tumor volume was 0.5 cm3. Median PI-RADS and ISUP of index lesions were 4 and 3, respectively. Index lesions were visible in grayscale US and ANNA in 25 cases (57%) and 30 cases (68%), respectively. Combining CT-US-ANNA, we detected index lesions in 35 patients (80%). Conclusions: The first results of multiparametric CT-US-ANNA imaging showed promising detection rates in patients with csPC. US imaging with ANNA has the potential to complement PC diagnosis.

Purpose To investigate the impact of rectal spacing on inter‐fractional rectal and bladder dose and the need for adaptive planning in prostate cancer patients undergoing SBRT with a 0.35 T MRI‐Linac. Materials and Methods We evaluated and compared SBRT plans from prostate cancer patients with and without rectal spacer who underwent treatment on a 0.35 T MRI‐Linac. Each group consisted of 10 randomly selected patients that received prostate SBRT to a total dose of 36.25 Gy in five fractions. Dosimetric differences in planned and delivered rectal and bladder dose and the number of fractions violating OAR constraints were quantified. We also assessed whether adaptive planning was needed to meet constraints for each fraction. Results On average, rectal spacing reduced the maximum dose delivered to the rectum by more than 8 Gy (p

Performing minimal invasive interventions under real-time image guidance proves problematic in a closed-bore magnetic resonance imaging scanner. To enable better usability in MRI guided interventions, robotic systems could be used for additional assistance. However, the integration of such devices into the clinical workflow relates to many technical challenges in order to increase precision of the procedure while ensuring the overall safety. In this work, an MR compatible, compact, ultra-light and remotely controllable micropositioning system called μRIGS is presented. The instrument positioning unit can be operated in a 5-DoF range within a working volume of 2100 cm3with an instrument feed of 120 mm. The kinematics are actuated with a combination of non-metallic Bowden cables and electric stepper motors from a safe distance inside the scanner room, while their control is initiated from the control room via a custom-fitted GUI. Thereby, the precision of the positioning reproducibility of the respective DoF can be achieved with a mean deviation of 0.12 °. Furthermore, a feed force of 14 N can be provided to puncture various soft tissue.

Die multiparametrische Magnetresonanztomographie (mpMRT) der Prostata ist als entscheidender Bestandteil in der Fruherkennung und Ausbreitungsdiagnostik des primaren Prostatakarzinoms etabliert. Bildgestutzte Biopsieverfahren, wie die MRT-Ultraschall-Fusionsbiopsie, erlauben nicht nur die zielgerichtete Probengewinnung aus Indexlasionen zur Diagnosesicherung, sondern verbessern die Detektion klinisch signifikanter Prostatakarzinome. Minimal-invasive Therapieformen des lokalisierten Prostatakarzinoms erganzen das Behandlungsspektrum insbesondere fur Patienten mit niedrigem und mittlerem Risiko. Fur Patienten mit niedrigem bis mittlerem Risiko konnten die MRT-gestutzten, minimal-invasiven Therapieformen in Zukunft eine lokale Tumorkontrolle, verbesserte funktionelle Ergebnisse und die Moglichkeit einer spateren Therapieeskalation vereinen. Weitere Studienergebnisse in Bezug auf multimodale Ansatze sowie den Einsatz kunstlicher Intelligenz (KI) mittels Machine-Learning- und Deep-Learning-Algorithmen konnen zukunftig dabei helfen, das volle Potenzial fokaler Therapieansatze im Sinne der personalisierten Medizin auszuschopfen. Fur die einzelnen MRT-gestutzten minimal-invasiven Therapieverfahren ist der Abschluss laufender randomisierter Studien im Vergleich zur etablierten Ganzdrusentherapie erforderlich, bevor minimal-invasive Therapieformen Einzug in die klinischen Leitlinien finden. Dieser Ubersichtartikel beschaftigt sich mit minimal-invasiven Therapieverfahren des Prostatakarzinoms und der zentralen Rolle der mpMRT der Prostata in Therapieplanung und -durchfuhrung unter besonderer Berucksichtigung der Herausforderungen im klinischen Alltag.

Purpose To estimate the overall spatial distortion on clinical patient images for a 0.35 T MR‐guided radiotherapy system. Methods Ten patients with head‐and‐neck cancer underwent CT and MR simulations with identical immobilization. The MR images underwent the standard systematic distortion correction post‐processing. The images were rigidly registered and landmark‐based analysis was performed by an anatomical expert. Distortion was quantified using Euclidean distance between each landmark pair and tagged by tissue interface: bone‐tissue, soft tissue, or air‐tissue. For baseline comparisons, an anthropomorphic phantom was imaged and analyzed. Results The average spatial discrepancy between CT and MR landmarks was 1.15 ± 1.14 mm for the phantom and 1.46 ± 1.78 mm for patients. The error histogram peaked at 0–1 mm. 66% of the discrepancies were

Transcranial magnetic resonance-guided focused ultrasound (tMRgFUS) allows to perform incisionless thermoablation of deep brain structures. This feature makes it a very useful tool for the treatment of multiple neurological and psychiatric disorders. Currently, feedback of the thermoablation process is based on peak temperature readings assessed on real-time two-dimensional MRI thermometry. However, an accurate methodology relating thermal dosimetry with three-dimensional topography and temporal evolution of the lesion is still to be defined, thus hurdling the establishment of well-defined, evidence-based criteria to perform safe and effective treatments. In here we propose threshold-based thermoablation models to predict the volumetric topography of the lesion (whole lesion and necrotic core) in the short-to-mid-term based on thermal dosimetry estimated from intra-treatment MRI thermometry. To define and validate our models we retrospectively analyzed the data of sixty-three tMRgFUS thalamotomies for treating tremor. We used intra-treatment MRI thermometry to estimate whole-treatment three-dimensional thermal dose maps, defined either as peak temperature reached (Tmax) or thermal isoeffective dose (TID). Those maps were thresholded to find the dosimetric level that maximize the agreement (Sorensen-Dice coefficient - SDc) with the boundaries of the whole lesion and its core, assessed on T2w images 1-day (post-24h) and 3-months (post-3M) after treatment. Best predictions were achieved for the whole lesion at post-24h (SDc = 0.71), with Tmax /TID over 50.0 °C/90.5 CEM43. The core at post-24h and whole lesion at post-3M lesions reported a similar behavior in terms of shape accuracy (SDc ~0.35), and thermal dose thresholds ~55 °C/4100.0 CEM43. Finally, the optimal levels for post-3M core lesions were 55.5 °C/5800.0 CEM43 (SDc = 0.21). These thermoablation models could contribute to the real-time decision-making process and improve the outcome of tMRgFUS interventions both in terms of safety and efficacy.

Purpose To determine whether self-attention cycle-generative adversarial networks (cycle-GANs), a novel deep-learning method, can generate accurate synthetic computed tomography (sCT) to facilitate adaptive proton therapy in children with brain tumors. Materials and Methods Both CT and T1-weighted magnetic resonance imaging (MRI) of 125 children (ages 1-20 years) with brain tumors were included in the training dataset. A model introducing a self-attention mechanism into the conventional cycle-GAN was created to enhance tissue interfaces and reduce noise. The test dataset consisted of 7 patients (ages 2-14 years) who underwent adaptive planning because of changes in anatomy discovered on MRI during proton therapy. The MRI during proton therapy-based sCT was compared with replanning CT (ground truth). Results The Hounsfield unit-mean absolute error was significantly reduced with self-attention cycle-GAN, as compared with conventional cycle-GAN (65.3 ± 13.9 versus 88.9 ± 19.3, P Conclusion The novel cycle-GAN model with self-attention outperforms conventional cycle-GAN for children with brain tumors. Encouraging dosimetric results suggest that sCT generation can be used to identify patients who would benefit from adaptive replanning.

Although MR-guided radiotherapy (MRgRT) is advancing rapidly, generating accurate synthetic CT (sCT) from MRI is still challenging. Previous approaches using deep neural networks require large dataset of precisely co-registered CT and MRI pairs that are difficult to obtain due to respiration and peristalsis. Here, we propose a method to generate sCT based on deep learning training with weakly paired CT and MR images acquired from an MRgRT system using a cycle-consistent GAN (CycleGAN) framework that allows the unpaired image-to-image translation in abdomen and thorax. Data from 90 cancer patients who underwent MRgRT were retrospectively used. CT images of the patients were aligned to the corresponding MR images using deformable registration, and the deformed CT (dCT) and MRI pairs were used for network training and testing. The 2.5D CycleGAN was constructed to generate sCT from the MRI input. To improve the sCT generation performance, a perceptual loss that explores the discrepancy between high-dimensional representations of images extracted from a well-trained classifier was incorporated into the CycleGAN. The CycleGAN with perceptual loss outperformed the U-net in terms of errors and similarities between sCT and dCT, and dose estimation for treatment planning of thorax, and abdomen. The sCT generated using CycleGAN produced virtually identical dose distribution maps and dose-volume histograms compared to dCT. CycleGAN with perceptual loss outperformed U-net in sCT generation when trained with weakly paired dCT-MRI for MRgRT. The proposed method will be useful to increase the treatment accuracy of MR-only or MR-guided adaptive radiotherapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13534-021-00195-8.

Rationale and Objectives There have been multiple investigations defining and reporting the effectiveness of focal cryoablation as a treatment option for organ-confined prostate cancer. However, the impact of cryo-needle/probe placement accuracy within the tumor and gland has not been extensively studied. We analyzed how variations in the placement of the cryo-needles, specifically errors leading to incomplete ablation, may affect prostate cancer's resulting cryoablation. Materials and Methods We performed a study based on isothermal models using Monte Carlo simulations to analyze the impact of needle placement errors on tumor coverage and the probability of positive ablation margin. We modeled the placement error as a Gaussian noise on the cryo-needle position. The analysis used retrospective MRI data of 15 patients with biopsy-proven, unifocal, and MRI visible prostate cancer to calculate the impact of placement error on the volume of the tumor encompassed by the −40°C and −20°C isotherms using one to four cryo-needles. Results When the standard deviation of the placement error reached 3 mm, the tumor coverage was still above 97% with the −20°C isotherm, and above 81% with the −40°C isotherm using two cryo-needles or more. The probability of positive margin was significantly lower considering the −20°C isotherm (0.04 for three needles) than using the −40°C isotherm (0.66 for three needles). Conclusion The results indicated that accurate cryo-needle placement is essential for the success of focal cryoablation of prostate cancer. The analysis shows that an admissible targeting error depends on the lethal temperature considered and the number of cryo-needles used.

BACKGROUND: Opening the blood-brain barrier (BBB) with focused ultrasound and microbubbles (MBs) has potential use in non-invasive targeted therapy for central nervous system (CNS) diseases. Rapid short-pulse (RaSP) ultrasound with a microsecond sequence has been proposed as a minimally disruptive and efficient method for opening the BBB. This work aimed to test the feasibility and safety of BBB opening in a non-human primate model using combined RaSP ultrasound sequence and MBs. METHODS: The BBB of 2 rhesus macaques were opened with RaSP and the commonly used 10 millisecond long pulse (LP), combined with microbubble (SonoVueTM, 0.2 µL/g) injection in a bolus. The transducer’s central frequency was 300 kHz, and the acoustic pressure was set to 0.56 MPa calibrated in water. The BBB opening procedure was guided and evaluated with contrast-enhanced magnetic resonance imaging. The relative signal enhancement was compared between RaSP and LP sonication. T2-weighted fast-spin echo (FSE) and T2*-weighted gradient echo (GRE) sequences were scanned to evaluate edema and micro-bleeding at the end of the procedure. RESULTS: The relative signal enhancement was significantly higher (P

Purpose Magnetic resonance imaging (MRI)-guided transperineal prostate biopsy has been practiced since the early 2000s. The technique often suffers from targeting error due to deviation of the needle as a result of physical interaction between the needle and inhomogeneous tissues. Existing needle guide devices, such as a grid template, do not allow choosing an alternative insertion path to mitigate the deviation because of their limited degree-of-freedom (DoF). This study evaluates how an angulated needle insertion path can reduce needle deviation and improve needle placement accuracy. Methods We extended a robotic needle-guidance device (Smart Template) for in-bore MRI-guided transperineal prostate biopsy. The new Smart Template has a 4-DoF needle-guiding mechanism allowing a translational range of motion of 65 and 58 mm along the vertical and horizontal axis, and a needle rotational motion around the vertical and horizontal axis ± 30 ∘ and a vertical rotational range of - 30 ∘ , + 10 ∘ , respectively. We defined a path planning strategy, which chooses between straight and angulated insertion paths depending on the anatomical structures on the potential insertion path. We performed (a) a set of experiments to evaluate the device positioning accuracy outside the MR-bore, and (b) an in vivo experiment to evaluate the improvement of targeting accuracy combining straight and angulated insertions in animal models (swine, n = 3 ). Results We analyzed 46 in vivo insertions using either straight or angulated insertions paths. The experiment showed that the proposed strategy of selecting straight or angulated insertions based on the subject's anatomy outperformed the conventional approach of just straight insertions in terms of targeting accuracy (2.4 mm [1.3-3.7] vs 3.9 mm [2.4-5.0] {Median IQR } ); p = 0.041 after the bias correction). Conclusion The in vivo experiment successfully demonstrated that an angulated needle insertion path could improve needle placement accuracy with a path planning strategy that takes account of the subject-specific anatomical structures.

We present the first case in the literature of a patient with a histology-proven intimal sarcoma of the heart, recurrent after surgery, treated with stereotactic MR-guided online adaptive radiation therapy on an MR-Linac machine. The treatment was feasible and well tolerated. The CT scan 6 months after the last treatment showed stable disease.

Highlights • Adapt-to-Shape (ATS) workflows enable high-precision MR-guided radiotherapy. • Online, manual contour adaptation is a time-consuming step in the ATS workflow. • Trained radiation therapists adapt contours for prostate cancer treatment. • CTV contours by radiation therapists are well-suited for MR-Linac prostate cancer treatment., Background and purpose Magnetic resonance (MR)-guided linear accelerator (MR-Linac) systems have changed radiotherapy workflows. The addition of daily online contour adaptation allows for higher precision treatment, but also increases the workload of those involved. We train radiation therapists (RTTs) to perform daily online contour adaptation for MR-Linac treatment of prostate cancer (PCa) patients. The purpose of this study was to evaluate these prostate contours by performing an interfraction and interobserver analysis. Materials and methods Clinical target volume (CTV) contours generated online by RTTs from 30 low-intermediate risk PCa patients, treated with 5x7.25 Gy, were used. Two physicians (Observers) judged the RTTs contours and performed adaptations when necessary. Interfraction relative volume differences between the first and the subsequent fractions were calculated for the RTTs, Observer 1, and Observer 2. Additionally, interobserver dice’s similarity coefficient (DSC) for fraction 2–5 was calculated with the RTTs- and physician-adapted contours. Clinical acceptability of the RTTs contours was judged by a third observer. Results Mean (SD) online contour adaptation time was 12.6 (±3.8) minutes and overall median (interquartile range [IQR]) relative volume difference was 9.3% (4.4–13.0). Adaptations by the observers were mostly performed at the apex and base of the prostate. Median (IQR) interobserver DSC between RTTs and Observer 1, RTTs and Observer 2, and Observer 1 and 2 was 0.99 (0.98–1.00), 1.00 (0.98–1.00), and 1.00 (0.99–1.00), respectively. Contours were acceptable for clinical use in 113 (94.2%) fractions. Dose-volume histogram (DVH) analysis showed significant CTV underdosage for one of the seven identified outliers. Conclusion Daily online contour adaptation by RTTs is clinically feasible for MR-Linac treatment of PCa.

espanolObjetivo Describir las tecnicas «radioguided occult lesion localization» (ROLL) y «sentinel node occult lesion localization» (SNOLL) guiadas por resonancia magnetica (RM) para el marcaje de restos tumorales en pacientes con cancer infiltrante de mama que han recibido quimioterapia neoadyuvante y presentar los resultados quirurgicos y la supervivencia libre de enfermedad. Material y metodo Estudio observacional prospectivo de 132 pacientes correspondientes a 136 tumores, tratadas con quimioterapia neoadyuvante en nuestro hospital entre los anos 2011 a 2017 y marcadas preoperatoriamente con ROLL/SNOLL guiado con RM. Se describieron los aspectos tecnicos de localizacion del lecho tumoral residual y se registraron variables correspondientes a los procedimientos quirurgicos y eventos ocurridos durante el seguimiento. Resultados La mediana de tamano tumoral fue 20,5 mm (rango intercuartilico [RIC]:14 a 28). El 96,3% eran carcinomas ductales infiltrantes. La tasa de deteccion del ganglio centinela fue 98,9% y se obtuvo respuesta completa patologica (RCP) en el 58,1%. La tasa de bordes afectos en los 89 casos operados mediante cirugia conservadora fue del 2,2%. Con una mediana de seguimiento de 50 meses (RIC: 37 a 61) se observo un 7,4% de recaidas, siete locorregionales y tres a distancia. La media estimada de supervivencia libre de enfermedad fue de 83,2 meses (Intervalo de Confianza [IC] 95%: 79,6 a 86,6). Conclusiones La tecnica ROLL/SNOLL guiada con RM es util en el marcaje de los restos tumorales tras neoadyuvancia, proporcionando unos resultados quirurgicos adecuados y un buen control locorregional. EnglishPurpose To describe the results of MRI (magnetic resonance image) guided ROLL (radioguided occult lesion localization) and SNOLL (sentinel node occult lesion localization) in the localization of residual disease after neoadjuvant chemotherapy for breast cancer, as well as assessing the surgical results obtained and disease free survival. Methods Prospective observational analysis of 132 patients with 136 tumors, treated with neoadjuvant chemotherapy at our hospital between 2011-2017. Residual disease was located presurgically with MRI guided ROLL/SNOLL technique. We analyzed technical aspects of localization, and variables corresponding to surgical procedures and events occurred during follow-up. Results The median tumor size was of 20.5mm (interquartilic range [IQR]: 14-28). The majority (96.3%) were invasive ductal carcinomas. Sentinel lymph node detection rate was 98.9%. Complete pathological response (CPR) in the breast was achieved in 58.1% of cases. The rate of affected margins in 89 cases operated by conservative surgery was 2.2%. With a median follow-up of 50 months (IQR: 37-61) we found a 7.4% rate of relapses. Of these, seven were loco-regional and three at distant sites. The estimated mean of disease-free survival time was 83.2 months (Confidence Interval [CI] 95%: 79.6-86.6). Conclusions MRI guided ROLL/SNOLL is a great tool for breast cancer residual disease localization following neoadjuvant chemotherapy. In addition, this technique attains good loco-regional control of the diseases and has excellent surgical results.

Radiation therapy (RT) continues to be one of the mainstays of cancer treatment. Considerable efforts have been recently devoted to integrating MRI into clinical RT planning and monitoring. This integration, known as MRI-guided RT, has been motivated by the superior soft-tissue contrast, organ motion visualization, and ability to monitor tumor and tissue physiologic changes provided by MRI compared with CT. Offline MRI is already used for treatment planning at many institutions. Furthermore, MRI-guided linear accelerator systems, allowing use of MRI during treatment, enable improved adaptation to anatomic changes between RT fractions compared with CT guidance. Efforts are underway to develop real-time MRI-guided intrafraction adaptive RT of tumors affected by motion and MRI-derived biomarkers to monitor treatment response and potentially adapt treatment to physiologic changes. These developments in MRI guidance provide the basis for a paradigm change in treatment planning, monitoring, and adaptation. Key challenges to advancing MRI-guided RT include real-time volumetric anatomic imaging, addressing image distortion because of magnetic field inhomogeneities, reproducible quantitative imaging across different MRI systems, and biologic validation of quantitative imaging. This review describes emerging innovations in offline and online MRI-guided RT, exciting opportunities they offer for advancing research and clinical care, hurdles to be overcome, and the need for multidisciplinary collaboration. (C) RSNA, 2020

Theranostic agents based on magnetic resonance imaging (MRI) and photothermal therapy (PTT) play an important role in tumor therapy. However, the available theranostic agents are facing great challenges such as biocompatibility, MRI contrast effect and photothermal conversion efficiency (η). In this work, mesoporous polydopamine nanoparticles (MPDAPs/Mn) were prepared on MRI and PTT combined theranostic nanoplatforms, of which the high loading manganese ions and specific surface areas enable good MRI contrast and excellent photothermal conversion efficiency, respectively. The MPDAPs/Mn have uniform morphology, good stability and biocompatibility. Meanwhile, in vitro and in vivo studies have confirmed their superior T1-weighted MRI effect and photothermal conversion efficiency. Furthermore, MPDAPs/Mn have excellent antitumor efficacy in HeLa tumor-bearing mice. Therefore, this developed MPDAPs/Mn theranostic nanoplatform could be a promising candidate for MRI-guided photothermal cancer therapy.

Highlights • Deliverable plans for 1 and 2 fraction SBRT can be created for the Unity MR-Linac. • Dose constraints and objectives from HDR and SBRT clinical studies were applied. • In 40% of 1 and 2 fraction plans target doses were compromised to meet OAR goals., The drive towards hypofractionated prostate radiotherapy is motivated by a low alpha/beta ratio for prostate cancer (1 to 3 Gy) compared to surrounding organs at risk, implying an improved therapeutic ratio with increasing dose per fraction. Early evidence from studies of ultrahypofractionated (UHF) prostate HDR brachytherapy has shown good tolerability in terms of normal tissue toxicities and clinical outcomes similar to conventional fractionation schedules. MR-guided stereotactic body radiotherapy (SBRT) with online plan adaptation and real-time tumour imaging may enable UHF doses to be delivered to the prostate safely, without the invasiveness of brachytherapy. The feasibility of UHF prostate treatment planning for the Unity MR-Linac (MRL, Elekta AB, Stockholm) was investigated for target prescriptions and planning constraints derived from the HDR brachytherapy and SBRT literature. Monaco 5.40 (Elekta) was used to generate MRL step-and-shoot IMRT plans for three dose fractionation protocols (5, 2 and 1 fractions), for ten randomly selected previously treated prostate cancer patients. Of the ten plans per UHF scheme, all clinical goals were met in all cases for 5 fractions, and in six cases for both 2 and 1 fraction schemes. PTV D95% was compromised by up to 6.4% and 3.9% of the associated target dose for 2 and 1 fraction plans respectively. There were two cases of PTV D95% compromise greater than a 5% dose decrease for the 2 fraction plans. The study suggests feasibility of the UHF treatment planning approaches if combined with real-time motion mitigation strategies.

Magnetic resonance-guided focused ultrasound is a powerful new technology that is enabling development of noninvasive applications for complex brain disorders. This is currently revolutionizing the treatment of tremor disorders, and a variety of experimental applications are under active investigation. To fully realize the potential of this disruptive technology, many challenges have been identified, some of which have been addressed and others remain to be solved. As an image-based technology, optimal intraoperative imaging can be difficult to achieve and several factors can influence the quality of these images. Technical issues with current devices can also limit the effective delivery of ultrasound technology to particular targets. While lesioning is the primary approved application of magnetic resonance-guided focused ultrasound at present, the ability to transient and precisely open the blood-brain barrier has the potential to clear brain pathologies and deliver restorative therapies, but this more experimental method presents unique difficulties to overcome. Finally, regulatory and reimbursement hurdles currently remain complex and continue to limit widespread application of even approved, effective applications. Here we review many of these challenges, discuss several solutions that have already been developed, and propose potential options for addressing some of these complexities in the future.

Purpose Hepatic recurrence of liver malignancies is a leading problem in patients after liver resection with curative intention. Thermoablation is a promising treatment approach for patients after hepatic resection, especially in liver-limited conditions. This study aimed to investigate safety, survival, and local tumor control rates of MRI-guided percutaneous thermoablation of recurrent hepatic malignancies following hepatic resection. Material and methods Data from patients with primary or secondary hepatic malignancies treated between 2004 and 2018 with MRI-guided percutaneous thermoablation of hepatic recurrence after prior hepatic resection were retrospectively analyzed. Disease-free survival and overall survival rates were calculated using the Kaplan-Meier method. Results A total of 57 patients with hepatic recurrence (mean tumor size = 18.9 ± 9.1 mm) of colorectal cancer liver metastases (n = 27), hepatocellular carcinoma (n = 17), intrahepatic recurrence of cholangiocellular carcinoma (n = 9), or other primary malignant tumor entities (n = 4) were treated once or several times with MR-guided percutaneous radiofrequency (n = 52) or microwave ablation (n = 5) (range: 1–4 times). Disease progression occurred due to local recurrence at the ablation site in nine patients (15.8%), non-local hepatic recurrence in 33 patients (57.9%), and distant malignancy in 18 patients (31.6%). The median overall survival for the total cohort was 40 months and 49 months for the colorectal cancer group, with a 5-year overall survival rate of 40.7 and 42.5%, respectively. The median disease-free survival was 10 months for both the total cohort and the colorectal cancer group with a 5-year disease-free survival rate of 15.1 and 14.8%, respectively. The mean follow-up time was 39.6 ± 35.7 months. Conclusion MR-guided thermoablation is an effective and safe approach in the treatment of hepatic recurrences in liver-limited conditions and can achieve long-term survival.

The diagnosis and management of prostate cancer involves the interpretation of data from multiple modalities to aid in decision making. Tools like PSA levels, MRI guided biopsies, genomic biomarkers, and Gleason grading are used to diagnose, risk stratify, and then monitor patients during respective follow-ups. Nevertheless, diagnosis tracking and subsequent risk stratification often lend itself to significant subjectivity. Artificial intelligence (AI) can allow clinicians to recognize difficult relationships and manage enormous data sets, which is a task that is both extraordinarily difficult and time consuming for humans. By using AI algorithms and reducing the level of subjectivity, it is possible to use fewer resources while improving the overall efficiency and accuracy in prostate cancer diagnosis and management. Thus, this systematic review focuses on analyzing advancements in AI-based artificial neural networks (ANN) and their current role in prostate cancer diagnosis and management.

Nanoparticle-mediated photothermal therapy (PTT) has shown promising capability for tumor therapy through the high local temperature at the tumor site generated by a photothermal agent (PTA) under visible or near-infrared (NIR) irradiation. Improving the accumulation of PTA at the tumor site is crucial to achieving effective photothermal treatment. Here, we developed temperature-activatable engineered neutrophils (Ne) by combining indocyanine green (ICG)-loaded magnetic silica NIR-sensitive nanoparticles (NSNP), which provide the potential for dual-targeted photothermal therapy. The combined effect of neutrophil targeting and magnetic targeting increased the accumulation of PTA at the tumor site. According to magnetic resonance imaging (MRI), the retention of intravenous injected NSNP-incorporated neutrophils within the tumor site was markedly augmented as compared to free NSNP. Furthermore, when irradiated by NIR, NSNP could cause a high local temperature at the tumor site and the thermal stimulation of neutrophils. The heat can kill tumor cells directly, and also lead to the death of neutrophils, upon which active substances with tumor-killing efficacy will be released to kill residual tumor cells and thus reduce tumor recurrence. Thereby, our therapy achieved the elimination of malignancy in the mouse model of the pancreatic tumor without recurrence. Given that all materials used in this system have been approved for use in humans, the transition of this treatment method to clinical application is plausible.

Discrepancies between the needle feature position on magnetic resonance imaging (MRI) and the underlying physical needle position could increase localization errors during needle-based targeting procedures in MRI-guided percutaneous interventions. This work aimed to develop a deep learning-based framework to automatically localize the physical needle position using only the needle features on MR images. Physics-based simulations were performed to generate single-slice and 3-slice images with needle features from a range of underlying needle positions and MRI parameters to form datasets for training single-slice and 3-slice Mask Region-Based Convolutional Neural Network (R-CNN) models for physical needle localization. Ex vivo tissue images were combined with simulated needle features for fine-tuning. Next, the physics-driven Mask R-CNN models were combined with a previously developed Mask R-CNN model for needle feature localization to form an automated framework to localize the physical needle. To test the accuracy of the proposed framework, both single-slice and 3-slice MRI data were acquired from needle insertion experiments in ex vivo tissue phantoms. Using the single-slice model, the proposed framework achieved sub-millimeter physical needle localization accuracy on single-slice images aligned with the needle. The fine-tuning step reduced in-plane physical needle tip localization error (mean±standard deviation) to 0.96±0.69 mm in ex vivo tissue data. The 3-slice model further reduced the through-plane physical needle tip localization error to 2.3±1.1 mm in situations where the imaging plane may be misaligned with the needle. The processing time of the framework using both models was 200 ms per frame. The proposed framework can achieve physical needle localization in real time to support MRI-guided interventions.

Background: Specimen radiography is important for the biopsy of breast microcalcifications, and MRI is limited in the detection of microcalcifications. It is unknown whether or not the presence of microcalcifications on MRI-guided biopsies is significant. Purpose: To determine whether specimen radiography of MRI-guided biopsy samples provides any added benefits in tissue assessment. Materials and Methods: This is an IRB-approved, HIPPA-compliant retrospective review of MRI-guided biopsy reports whose tissue underwent specimen radiography from 2010 to 2017. Pathology reports were queried to compare samples with and without calcium and reviewed to determine if calcifications correlated with the lesion of interest. If there was a correlation, the original MRI was reviewed. Final pathology reports were also reviewed if excision was performed. Results: A total of 889 patients ages 22 - 85 were included with 140 (15.7%, 140/889) containing calcifications. Of 140 specimens, 119 (85.0%, 119/140) cases separated the calcifications. A total of 41 (34.5%, 41/119) were malignant or high-risk lesions/atypia of which 15 (36.6%, 15/41) showed a higher-grade lesion in the specimen containing calcium. Out of these 15, 4 (26.7%, 4/15) were pathologically associated with calcium; however, pathologic diagnosis was not dependent on the presence of calcifications. All 4 were high-risk lesions and none were malignancies. MRI in these cases showed three enhancing masses and one non-mass enhancement. None were upgraded at excision. Conclusion: The presence of microcalcifications on MRI-guided biopsies does not aid in tissue assessment and does not impact pathologic diagnosis. Specimen radiography provides no added benefits in the setting of MRI-guided biopsies.

Background Trans-cranial MR guided focused ultrasound (tcMRgFUS) ablation targets are

Magnetic resonance-guided focused ultrasound (MRgFUS) is a cutting-edge technology that is changing the practice of movement disorders surgery. Given the noninvasive and innovative nature of this technology, there is great interest in expanding the use of MRgFUS to additional diseases and applications. Current approved applications target the motor thalamus to treat tremor, but clinical trials are exploring or plan to study noninvasive lesions with MRgFUS to ablate tumor cells in the brain as well as novel targets for movement disorders and brain regions associated with pain and epilepsy. Although there are additional potential indications for lesioning, the ability to improve function by destroying parts of the brain is still limited. However, MRgFUS can also be applied to a brain target after intravenous delivery of microbubbles to create cavitations and focally open the blood-brain barrier (BBB). This has already proven to be safe and technically feasible in human patients with Alzheimer's disease, and this action alone has potential to clear extracellular pathology associated with this and other neurodegenerative disorders. This also provides a foundation for noninvasive intravenous delivery of therapeutic molecules to precise brain targets after transient disruption of the BBB. Certain chemotherapies for brain tumors, immunotherapies, gene, and cell therapies are all examples of therapeutic or even restorative agents that normally will not enter the brain without direct infusion but which have been shown in preclinical studies to effectively traverse the BBB after transient disruption with MRgFUS. Here we will review these novel applications of MRgFUS to provide an overview of the extraordinary potential of this technology to expand future neurosurgical treatments of brain diseases.

Purpose The aim of this study was to assess the feasibility of T2 relaxation time in predicting the immediate technical outcome i.e., nonperfused volume ratio (NPVr) of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) treatment of symptomatic uterine fibroids and to compare it with existing T2-weighted imaging methods (Funaki classification and scaled signal intensity, SSI). Materials and methods 30 patients with 32 uterine fibroids underwent an MRI study including a quantitative T2 relaxation time measurement prior to MRgHIFU treatment. T2 relaxation times were measured with a multi-echo fast imaging-based technique with 16 echoes. The correlation between pretreatment values of the uterine fibroids and treatment outcomes, that is nonperfused volume ratios (NPVr), was assessed with nonparametric statistical measures. T2 relaxation time-based method was compared to existing T2-weighted imaging-based methods using receiver-operating-characteristics (ROC) curve analysis and Chi-square test. Results Nonparametric measures of association revealed a statistically significant negative correlation between T2 relaxation time values and NPVr. The T2 relaxation time classification (T2 I, T2 II, and T2 III) resulted in the whole model p-value of 0.0019, whereas the Funaki classification resulted in a p-value of 0.56. The T2 relaxation time classification (T2 I and T2 II) achieved a whole model of a p-value of 0.0024, whereas the SSI classification had a p-value of 0.0749. Conclusions A longer T2 relaxation time of the fibroid prior to treatment correlated with a lower NPVr. Based on our results, the T2 relaxation time classifications seem to outperform the Funaki classification and the SSI method.

Objective To develop a thermochromic tissue-mimicking phantom (TTMP) with an embedded 3D-printed bone mimic of the lumbar spine to evaluate MRgFUS ablation of the facet joint and medial branch nerve. Materials and methods Multiple 3D-printed materials were selected and characterized by measurements of speed of sound and linear acoustic attenuation coefficient using a through-transmission technique. A 3D model of the lumbar spine was segmented from a de-identified CT scan, and 3D printed. The 3D-printed spine was embedded within a TTMP with thermochromic ink color change setpoint at 60 °C. Multiple high energy sonications were targeted to the facet joints and medial branch nerve anatomical location using an ExAblate MRgFUS system connected to a 3T MR scanner. The phantom was dissected to assess sonication targets and the surrounding structures for color change as compared to the expected region of ablation on MR-thermometry. Results The measured sound attenuation coefficient and speed of sound of gypsum was 240 Np/m-MHz and 2471 m/s, which is the closest to published values for cortical bone. Following sonication, dissection of the TTMP revealed good concordance between the regions of color change within the phantom and expected areas of ablation on MR-thermometry. No heat deposition was observed in critical areas, including the spinal canal and nerve roots from either color change or MRI. Conclusion Ablated regions in the TTMP correlated well with expected ablations based on MR-thermometry. These findings demonstrate the utility of an anatomic spine phantom in evaluating MRgFUS sonication for facet joint and medial branch nerve ablations.

Purpose This study assessed the therapeutic efficacy of postoperative magnetic resonance (MR)-guided interstitial 125 I seed implantation for treatment of oral and maxillofacial malignant tumors. Methods and materials A total of 127 patients with oral or maxillofacial malignant tumors were included in this study who received interstitial 125 I treatment after the surgery resection. Before implantation, all the patients received MR scans to assess the lesion scope, extent, and nature. 125 I implantation target regions were based on the pre-operative imaging. 125 I seeds were delivered to target regions via puncture needles under the real-time guidance of MR. Computed tomography (CT)or MR was performed immediately after implantation and again every 3 months later. Results After successful 125 I implantation, all patients were also examined regularly to detect tumor recurrence, lymphatic, and distant metastases. To date, CT or MR verification showed that 13/127 patients experienced tumor recurrence or lymphatic metastasis or distant metastasis. No seeds migration was observed, no serious treatment-related complications affected patient quality of life, and no important organ (such as major cervical vessels, spinal cord, etc.) injuries were observed. Conclusion Our results show that MR-guided 125 I implantation is an effective approach to site-specific treatment for oral and maxillofacial tumor, which could potentially reduce postoperative complications and tumor recurrence rates, increase patient survival, and improve quality of life.

Objective To evaluate compliance with short-interval follow-up MRI after benign concordant MRI-guided breast biopsy. Methods This institutional review board-approved retrospective study included all benign concordant MRI-guided biopsies performed between January 1, 2010, and May 1, 2018. The following was collected from the electronic medical record: patient and lesion characteristics, short-interval follow-up MRI recommendation, communication to referring physician, follow-up imaging, repeat biopsies, biopsy outcome, and patient insurance status. Compliance with recommendations was defined as follow-up MRI within 9 months of biopsy. Results Among 98 patients, there were 107 lesions with benign concordant MRI-guided biopsy results that met study criteria. After excluding 7 patients who underwent subsequent mastectomy, 50/91 (54.9%) patients were recommended short-interval follow-up MRI. Of these, 33/50 (66.0%) had a short-interval follow-up MRI. Direct communication of the short-interval follow-up recommendation was documented in the biopsy report for 4/50 (8%) patients. Subsequent MRI was available for 77/107 (72%) lesions at a median of 29 months following MRI-guided biopsy (range, 3–96 months). Subsequent mammography was available for 21/30 (70%) remaining lesions at a median of 47 months following MRI-guided biopsy (range, 23–88 months). There were two repeat biopsies, with one subsequent malignancy, resulting in a false-negative rate of 0.9% (1/107). Conclusion When short-interval follow-up MRI was recommended following benign concordant MRI-guided breast biopsy, compliance was 66.0%. Lack of communication of the recommendation may at least partially explain the low compliance. The low false-negative rate (0.9%) suggests routine short-interval follow-up MRI may be unnecessary following benign concordant MRI-guided biopsy.

Purpose MR-linacs (MRLs) have enabled the use of stereotactic magnetic resonance (MR) guided online adaptive radiotherapy (SMART) across many cancers. As data emerges to support SMART, uncertainty remains regarding optimal technical parameters, such as optimal patient positioning, immobilization, image quality, and contouring protocols. Prior to clinical implementation of SMART, we conducted a prospective study in healthy volunteers (HVs) to determine optimal technical parameters and to develop and practice a multidisciplinary SMART workflow. Methods HVs 18 years or older were eligible to participate in this IRB-approved study. Using a 0.35 T MRL, simulated adaptive treatments were performed by a multi-disciplinary treatment team in HVs. For each scan, image quality parameters were assessed on a 5-point scale (5 = extremely high, 1 = extremely poor). Adaptive recontouring times were compared between HVs and subsequent clinical cases with a t-test. Results 18 simulated treatments were performed in HVs on MRL. Mean parameters for visibility of target, visibility of nearby organs, and overall image quality were 4.58, 4.62, and 4.62, respectively (range of 4–5 for all measures). In HVs, mean ART was 15.7 min (range 4–35), comparable to mean of 16.1 (range 7–33) in the clinical cases (p = 0.8963). Using HV cases, optimal simulation and contouring guidelines were developed across a range of disease sites and have since been implemented clinically. Conclusions Prior to clinical implementation of SMART, scans of HVs on an MRL resulted in acceptable image quality and target visibility across a range of organs with similar ARTs to clinical SMART. We continue to utilize HV scans prior to clinical implementation of SMART in new disease sites and to further optimize target tracking and immobilization. Further study is needed to determine the optimal duration of HV scanning prior to clinical implementation.

Background Hypoxia is an important factor that contributes to chemoresistance and metastasis in triple negative breast cancer (TNBC), and alleviating hypoxia microenvironment can enhance the anti-tumor efficacy and also inhibit tumor invasion. Methods A near-infrared (NIR) responsive on-demand oxygen releasing nanoplatform (O2-PPSiI) was successfully synthesized by a two-stage self-assembly process to overcome the hypoxia-induced tumor chemoresistance and metastasis. We embedded drug-loaded poly (lactic-co-glycolic acid) cores into an ultrathin silica shell attached with paramagnetic Gd-DTPA to develop a Magnetic Resonance Imaging (MRI)-guided NIR-responsive on-demand drug releasing nanosystem, where indocyanine green was used as a photothermal converter to trigger the oxygen and drug release under NIR irradiation. Results The near-infrared responsive on-demand oxygen releasing nanoplatform O2-PPSiI was chemically synthesized in this study by a two-stage self-assembly process, which could deliver oxygen and release it under NIR irradiation to relieve hypoxia, improving the therapeutic effect of chemotherapy and suppressed tumor metastasis. This smart design achieves the following advantages: (i) the O2 in this nanosystem can be precisely released by an NIR-responsive silica shell rupture; (ii) the dynamic biodistribution process of O2-PPSiI was monitored in real-time and quantitatively analyzed via sensitive MR imaging of the tumor; (iii) O2-PPSiI could alleviate tumor hypoxia by releasing O2 within the tumor upon NIR laser excitation; (iv) The migration and invasion abilities of the TNBC tumor were weakened by inhibiting the process of EMT as a result of the synergistic therapy of NIR-triggered O2-PPSiI. Conclusions Our work proposes a smart tactic guided by MRI and presents a valid approach for the reasonable design of NIR-responsive on-demand drug-releasing nanomedicine systems for precise theranostics in TNBC. Graphical Abstract

Objective: To determine morphological and biological control as well as toxicity and quality of life (QoL) of men with localized prostate cancer (PCa) treated with MRI-guided focal boost radiotherapy. Material and Methods: 30 patients with PCa and a visible dominant intraprostatic lesion (DIL) identified on mpMRI were included in a prospective Phase II trial. Matching point registration of planning CT and T2W, diffusion-weighted and a gradient-recalled echo (GRE) MRI images made in treatment position was used for prostate and tumour delineation. Treatment consisted on 35 daily fractions of 2.17 Gy with a concomitant focal boost to the DIL of 2.43 Gy using volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with intraprostatic fiducial markers. Biochemical failure was analysed using PSA nadir +2 ng/mL criteria and local control using mpMRI evaluation at 6–9 months following RT. Acute and late toxicity were defined according to CTCAE v.4.0 and RTOG/EORTC scales and QoL was assessed using IPSS, EPIC short-form and UCLA-PCI questionnaires. Results: The median radiation dose to the prostate was 77.6 Gy (IQR 77.3–78.1), and to the DIL was 85.5 Gy (IQR 85.0–86.0). With a median follow up of 30.0 months (IQR 25.5–40.27), all patients remain free of biochemical relapse. An mpMRI complete response was observed in 25 patients during the first post-treatment evaluation at 6 months. The remaining five patients achieved a complete disappearance of the DIL both on T2 and DWI on the second mpMRI performed at 9 months following treatment. Six out of 30 (20%) patients presented acute Grade 2 urinary toxicity with no Grade 3 acute complications. Acute rectal toxicity was only found in 2 (6.6%) patients (both Grade 1). Only late Grade 1 urinary and rectal complications were observed in 3/30 patients, respectively, with no Grade 2 or more late toxicity. The urinary, bowel and sexual bother EPIC scores were slightly and insignificantly increased in the first 3 months post-treatment, returning to normal afterwards. Conclusions: mpMRI-guided focal boost using VMAT hypofractionated technique is associated with an excellent morphological and functional response control and a safe toxicity profile. Advances in knowledge: In the present trial, we examined the potential role of mpMRI for radiological assessment (functional and morphological) of treatment response in high-risk prostate cancer patients treated with MRI-guided focal radiotherapy dose intensification to dominant Intraprostatic lesion.