Receive coil quality assurance procedure and automated analysis for ViewRay MRIdian MR-Linac.

PURPOSE: Regular receiving coil quality assurance (QA) is required to ensure image quality of an MRIdian Linac system. The manufacturer provides a spherical phantom and positioning tube for single-slice signal-to-noise ratio (SNR) and uniformity assessments. We aimed to improve imaging setup and coverage and eliminate inter-scan variability by employing multi-slice imaging of a stable phantom. Additionally, we strived to expedite analysis by developing objective, automated analysis software. METHODS: A 5300 mL cylindrical plastic bottle placed in plastic bins was scanned at isocenter using a spin-echo sequence with NEMA-recommended parameters and 18 axial slices, avoiding phantom repositioning. Acquisition was repeated with and without prescan normalization filtering and by saving uncombined element images. Obtained data were analyzed using custom open-source MATLAB code. Signal and noise images were automatically assigned, and ROIs for SNR and uniformity calculations were defined using image thresholding. SNR and uniformity pass/fail decisions were made using baseline comparisons. RESULTS: The proposed method was successfully implemented as monthly coil QA for 3.5 years. Setup and scanning took 41 min on average for a coil set. Automated image analysis was completed in a few minutes. Signal intensity peaked around +90 or -90 mm for Torso or Head/Neck coil unfiltered images. Noise peaked and minimized SNR inside ±30 mm from isocenter, while maximizing it around ±130 mm. Prescan normalization smoothed signal response, reduced SNR and increased uniformity. Individual coil element image analysis identified their position, signal or noise response and SNR. SNR and uniformity pass/fail thresholds were set for already tested and new coils. Conspicuous and subtle Torso coil malfunctions were detected considering baseline deviations of combined and individual element results. CONCLUSIONS: Our QA method eliminated observer bias and provided insights into coil function, image filtering performance and coil element location. It provided SNR and uniformity thresholds and identified faulty coil elements.

Image quality comparisons of coil setups in 3T MRI for brain and head and neck radiotherapy simulations.

PURPOSE: MRI is increasingly used for brain and head and neck radiotherapy treatment planning due to its superior soft tissue contrast. Flexible array coils can be arranged to encompass treatment immobilization devices, which do not fit in diagnostic head/neck coils. Selecting a flexible coil arrangement to replace a diagnostic coil should rely on image quality characteristics and patient comfort. We compared image quality obtained with a custom UltraFlexLarge18 (UFL18) coil setup against a commercial FlexLarge4 (FL4) coil arrangement, relative to a diagnostic Head/Neck20 (HN20) coil at 3T. METHODS: The large American College of Radiology (ACR) MRI phantom was scanned monthly in the UFL18, FL4, and HN20 coil setup over 2 years, using the ACR series and three clinical sequences. High-contrast spatial resolution (HCSR), image intensity uniformity (IIU), percent-signal ghosting (PSG), low-contrast object detectability (LCOD), signal-to-noise ratio (SNR), and geometric accuracy were calculated according to ACR recommendations for each series and coil arrangement. Five healthy volunteers were scanned with the clinical sequences in all three coil setups. SNR, contrast-to-noise ratio (CNR) and artifact size were extracted from regions-of-interest along the head for each sequence and coil setup. For both experiments, ratios of image quality parameters obtained with UFL18 or FL4 over those from HN20 were formed for each coil setup, grouping the ACR and clinical sequences. RESULTS: Wilcoxon rank-sum tests revealed significantly higher (p < 0.001) LCOD, IIU and SNR, and lower PSG ratios with UFL18 than FL4 on the phantom for the clinical sequences, with opposite PSG and SNR trends for the ACR series. Similar statistical tests on volunteer data corroborated that SNR ratios with UFL18 (0.58 ± 0.19) were significantly higher (p < 0.001) than with FL4 (0.51 ± 0.18) relative to HN20. CONCLUSIONS: The custom UFL18 coil setup was selected for clinical application in MR simulations due to the superior image quality demonstrated on a phantom and volunteers for clinical sequences and increased volunteer comfort.

Lung volume reproducibility under ABC control and self-sustained breath-holding.

An Active Breathing Coordinator (ABC) can be employed to induce breath-holds during CT imaging and radiotherapy of lung, breast and liver cancer, and recently during lung cancer MRI. The apparatus measures and controls respiratory volume, hence subject lung volume reproducibility is its principal measure of effectiveness. To assess ABC control quality, the intra-session reproducibility of ABC-induced lung volumes was evaluated and compared with that reached by applying the clinical standard of operator-guided self-sustained breath-holds on healthy volunteers during MRI. Inter-session reproducibility was investigated by repeating ABC-controlled breath-holds on a second visit. Additionally, lung volume agreement with ABC devices used with different imaging modalities in the same institution (MR, CT), or for a breast trial treatment, was assessed. Lung volumes were derived from three-dimensional (3D) T1-weighted MRI datasets by three observers employing semiautomatic lung delineation on a radiotherapy treatment planning system. Inter-observer variability was less than 6% of the delineated lung volumes. Lung volume agreement between the different conditions over all subjects was investigated using descriptive statistics. The ABC equipment dedicated for MR application exhibited good intra-session and inter-session lung volume reproducibility (1.8% and 3% lung volume variability on average, respectively). MR-assessed lung volumes were similar using different ABC equipment dedicated to MR, CT, or breast radiotherapy. Overall, lung volumes controlled by the same or different ABC devices agreed better than with self-controlled breath-holds, as suggested by the average ABC variation of 1.8% of the measured lung volumes (99 mL), compared to the 4.1% (226 mL) variability observed on average with self-sustained breath-holding.

Exploration of the neural correlates of ticklish laughter by functional magnetic resonance imaging.

The burst of laughter that is evoked by tickling is a primitive form of vocalization. It evolves during an early phase of postnatal life and appears to be independent of higher cortical circuits. Clinicopathological observations have led to suspicions that the hypothalamus is directly involved in the production of laughter. In this functional magnetic resonance imaging investigation, healthy participants were 1) tickled on the sole of the right foot with permission to laugh, 2) tickled but asked to stifle laughter, and 3) requested to laugh voluntarily. Tickling that was accompanied by involuntary laughter activated regions in the lateral hypothalamus, parietal operculum, amygdala, and right cerebellum to a consistently greater degree than did the 2 other conditions. Activation of the periaqueductal gray matter was observed during voluntary and involuntary laughter but not when laughter was inhibited. The present findings indicate that hypothalamic activity plays a crucial role in evoking ticklish laughter in healthy individuals. The hypothalamus promotes innate behavioral reactions to stimuli and sends projections to the periaqueductal gray matter, which is itself an important integrative center for the control of vocalization. A comparison of our findings with published data relating to humorous laughter revealed the involvement of a common set of subcortical centers.

Feasibility and clinical implementation of MRI-guided surface brachytherapy.

Purpose: Best practices for high-dose-rate surface applicator brachytherapy treatment (SABT) have long relied on computed tomography (CT)-based imaging to visualize diseased sites for treatment planning. Compared with magnetic resonance (MR)-based imaging, CT provides insufficient soft tissue contrast. This work described the feasibility of clinical implementation of MR-based imaging in SABT planning to provide individualized treatment optimization. Material and methods: A 3D-printed phantom was used to fit Freiberg flap-style (Elekta, The Netherlands) applicator. Images were taken using an optimized pointwise encoding time reduction with radial acquisition (PETRA) MR sequence for catheter visualization, and a helical CT scan to generate parallel treatment plans. This clinical study included three patients undergoing SABT for Dupuytren's contracture/palmar fascial fibromatosis imaged with the same modalities.SABT planning was performed in Oncentra Brachy (Elekta Brachytherapy, The Netherlands) treatment planning software. A geometric analysis was conducted by comparing CT-based digitization with MR-based digitization. CT and MR dwell positions underwent a rigid registration, and average Euclidean distances between dwell positions were calculated. A dosimetric comparison was performed, including point-based dose difference calculations and volumetric segmentations with Dice similarity coefficient (DSC) calculations. Results: Euclidean distances between dwell positions from CT-based and MR-based plans were on average 0.68 ±0.05 mm and 1.35 ±0.17 mm for the phantom and patients, respectively. The point dose difference calculations were on average 0.92% for the phantom and 1.98% for the patients. The D95 and D90 DSC calculations were both 97.9% for the phantom, and on average 93.6% and 94.2%, respectively, for the patients. Conclusions: The sub-millimeter accuracy of dwell positions and high DSC's (> 0.95) of the phantom demonstrated that digitization was clinically acceptable, and accurate treatment plans were produced using MR-only imaging. This novel approach, MRI-guided SABT, will lead to individualized prescriptions for potentially improved patient outcomes.

Quantifying gadolinium-based nanoparticle uptake distributions in brain metastases via magnetic resonance imaging.

AGuIX, a novel gadolinium-based nanoparticle, has been deployed in a pioneering double-blinded Phase II clinical trial aiming to assess its efficacy in enhancing radiotherapy for tumor treatment. This paper moves towards this goal by analyzing AGuIX uptake patterns in 23 patients. A phantom was designed to establish the relationship between AGuIX concentration and longitudinal ( T 1 ) relaxation. A 3T MRI and MP2RAGE sequence were used to generate patient T 1 maps. AGuIX uptake in tumors was determined based on longitudinal relaxivity. AGuIX (or placebo) was administered to 23 patients intravenously at 100 mg/kg 1-5 hours pre-imaging. Each of 129 brain metastases across 23 patients were captured in T 1 maps and examined for AGuIX uptake and distribution. Inferred AGuIX recipients had average tumor uptakes between 0.012 and 0.17 mg/ml, with a mean of 0.055 mg/ml. Suspected placebo recipients appeared to have no appreciable uptake. Tumors presented with varying spatial AGuIX uptake distributions, suspected to be related to differences in accumulation time and patient-specific bioaccumulation factors. This research demonstrates AGuIX's ability to accumulate in brain metastases, with quantifiable uptake via T 1 mapping. Future analyses will extend these methods to complete clinical trial data (~ 134 patients) to evaluate the potential relationship between nanoparticle uptake and possible tumor response following radiotherapy.Clinical Trial Registration Number: NCT04899908.Clinical Trial Registration Date: 25/05/2021.

Neural correlates of creative writing: an fMRI study.

Cerebral activations involved in actual writing of a new story and the associated correlates with creative performance are still unexplored. To investigate the different aspects of the creative writing process, we used functional magnetic resonance imaging while 28 healthy participants performed a new paradigm related to creative writing: "brainstorming" (planning a story) and "creative writing" (writing a new and creative continuation of a given literary text), as well as an additional control paradigm of "reading" and "copying." Individual verbal creativity was assessed with a verbal creativity test and creative performance with a qualitative rating of the creative products. "brainstorming" engaged cognitive, linguistic, and creative brain functions mainly represented in a parieto-frontal-temporal network, as well as writing preparation, and visual and imaginative processing. "creative writing" activated motor and visual brain areas for handwriting and additionally, cognitive and linguistic areas. Episodic memory retrieval, free-associative and spontaneous cognition, and semantic integration were observed in a right lateralized activation pattern in bilateral hippocampi, bilateral temporal poles (BA 38), and bilateral posterior cingulate cortex in a "creative writing" minus "copying" comparison. A correlation analysis of "creative writing" minus "copying" with the creativity index revealed activation in the left inferior frontal gyrus (BA 45) and the left temporal pole (BA 38). Thus, verbal creativity during "creative writing" is associated with verbal and semantic memory as well as semantic integration.

Catheter reconstruction and dosimetric verification of MRI-only treatment planning (MRTP) for interstitial HDR brachytherapy using PETRA sequence.

Objective. The feasibility of MRI-only treatment planning (MRTP) for interstitial high-dose rate (HDR) brachytherapy (BT) was investigated for patients diagnosed with gynecologic cancer.Approach. A clinical MRTP workflow utilizing a 'pointwise encoding time reduction with radial acquisition (PETRA)' sequence was proposed. This is a clinically available MRI sequence optimized to improve interstitial catheter-tissue contrast. Interstitial needles outside the obturator region were reconstructed using MR images only. For catheters penetrating through the obturator, a library-based reconstruction was proposed. In this work, dwell coordinates from the clinical CT-based reconstruction were used as the surrogate for the library-based approach. For MR-only plan, dwell times were activated and assigned as in the clinical plans. The catheter reconstruction was assessed by comparing dwell position coordinates. The dosimetric comparisons between a clinical plan and MR-only plan were assessed for physical and EQD2 dose and volume parameters forD90,D50andD98for clinical target volume (CTV) andD2cc,D0.1ccandD5ccfor OARs.Main results. Catheter reconstruction was possible using the optimized PETRA sequence on MR images. An overall reconstruction difference of 1.7 ± 0.5 mm, attributed to registration-based errors, was found compared to the CT-based reconstruction. The MRTP workflow has the potential to generate a treatment plan with an equivalent dosimetric quality compared to the conventional CT/MRI-based approach. For CTVD90, physical and EQD2 dose and volume parameter differences were 1.5 ± 1.9% and 0.7 ± 1.0 Gy, respectively. ForD2ccOARs, DVH (EQD2) differences were -0.4 ± 1.1% (-0.2 ± 0.5 Gy), 0.5 ± 2.8% (0.2 ± 1.3 Gy) and -0.5 ± 1.4% (-0.2 ± 0.5 Gy) for rectum, bladder, and sigmoid, respectively.Significance. With the proposed MRTP approach, CT imaging may no longer be needed in HDR BT for interstitial gynecologic treatment. A proof-of-concept study was conducted to demonstrated that MRTP using PETRA is feasible, with comparable dosimetric results to the conventional CT/MRI-based approach.

Validation of an MR-based multimodal method for molecular composition and proton stopping power ratio determination using ex vivo animal tissues and tissue-mimicking phantoms.

Objective. Range uncertainty in proton therapy is an important factor limiting clinical effectiveness. Magnetic resonance imaging (MRI) can measure voxel-wise molecular composition and, when combined with kilovoltage CT (kVCT), accurately determine mean ionization potential (Im), electron density, and stopping power ratio (SPR). We aimed to develop a novel MR-based multimodal method to accurately determine SPR and molecular compositions. This method was evaluated in tissue-mimicking andex vivoporcine phantoms, and in a brain radiotherapy patient.Approach. Four tissue-mimicking phantoms with known compositions, two porcine tissue phantoms, and a brain cancer patient were imaged with kVCT and MRI. Three imaging-based values were determined: SPRCM(CT-based Multimodal), SPRMM(MR-based Multimodal), and SPRstoich(stoichiometric calibration). MRI was used to determine two tissue-specific quantities of the Bethe Bloch equation (Im, electron density) to compute SPRCMand SPRMM. Imaging-based SPRs were compared to measurements for phantoms in a proton beam using a multilayer ionization chamber (SPRMLIC).Main results. Root mean square errors relative to SPRMLICwere 0.0104(0.86%), 0.0046(0.45%), and 0.0142(1.31%) for SPRCM, SPRMM, and SPRstoich, respectively. The largest errors were in bony phantoms, while soft tissue and porcine tissue phantoms had <1% errors across all SPR values. Relative to known physical molecular compositions, imaging-determined compositions differed by approximately ≤10%. In the brain case, the largest differences between SPRstoichand SPRMMwere in bone and high lipids/fat tissue. The magnitudes and trends of these differences matched phantom results.Significance. Our MR-based multimodal method determined molecular compositions and SPR in various tissue-mimicking phantoms with high accuracy, as confirmed with proton beam measurements. This method also revealed significant SPR differences compared to stoichiometric kVCT-only calculation in a clinical case, with the largest differences in bone. These findings support that including MRI in proton therapy treatment planning can improve the accuracy of calculated SPR values and reduce range uncertainties.

Tuning ultrasmall theranostic nanoparticles for MRI contrast and radiation dose amplification.

Background: The introduction of magnetic resonance (MR)-guided radiation treatment planning has opened a new space for theranostic nanoparticles to reduce acute toxicity while improving local control. In this work, second-generation AGuIX® nanoparticles (AGuIX-Bi) are synthesized and validated. AGuIX-Bi are shown to maintain MR positive contrast while further amplifying the radiation dose by the replacement of some Gd3+ cations with higher Z Bi3+. These next-generation nanoparticles are based on the AGuIX® platform, which is currently being evaluated in multiple Phase II clinical trials in combination with radiotherapy. Methods: In this clinically scalable methodology, AGuIX® is used as an initial chelation platform to exchange Gd3+ for Bi3+. AGuIX-Bi nanoparticles are synthesized with three ratios of Gd/Bi, each maintaining MR contrast while further amplifying radiation dose relative to Bi3+. Safety, efficacy, and theranostic potential of the nanoparticles were evaluated in vitro and in vivo in a human non-small cell lung cancer model. Results: We demonstrated that increasing Bi3+ in the nanoparticles is associated with more DNA damage and improves in vivo efficacy with a statistically significant delay in tumor growth and 33% complete regression for the largest Bi/Gd ratio tested. The addition of Bi3+ by our synthetic method leads to nanoparticles that present slightly altered pharmacokinetics and lengthening of the period of high tumor accumulation with no observed evidence of toxicity. Conclusions: We confirmed the safety and enhanced efficacy of AGuIX-Bi with radiation therapy at the selected ratio of 30Gd/70Bi. These results provide crucial evidence towards patient translation.

First pointwise encoding time reduction with radial acquisition (PETRA) implementation for catheter detection in interstitial high-dose-rate (HDR) brachytherapy.

PURPOSE: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized to detect empty catheters in interstitial (HDR) brachytherapy with clinically acceptable spatial accuracy for the first time. Image quality and catheter detectability were assessed in phantoms, and the feasibility of PETRA's clinical implementation was assessed on a gynecological cancer patient. METHODS AND RESULTS: Empty catheters embedded in a gelatin phantom displayed positive signal on PETRA and more accurate cross-sections than on clinically employed T2-weighted sequences, differing by 0.4 mm on average from their nominal 2 mm diameter. PETRA presented minimal susceptibility differences and a symmetric metal artifact, contrary to the clinical sequences. The PETRA-CT catheter tip position differences assessed by a treatment planning system (TPS) were < 1 mm. PETRA also detected an interstitial template with empty catheters penetrating a poultry phantom and fused very well with CT. Interstitial catheter positional difference between PETRA and CT images was < 1 mm on average, increasing with distance from isocenter. All interstitial catheters and the employed interstitial template were detected on PETRA images of an endometrial adenocarcinoma patient. Empty needles were traceable using a TPS, with higher spatial resolution and more favorable contrast than on T2-weighted images used for contouring. A treatment plan could be produced by combining information from PETRA for catheter detection and from T2-weighted images for tumor and organs delineation. CONCLUSIONS: PETRA detected successfully and accurately interstitial catheters in phantoms. Its first clinical implementation shows a potential for MR-only treatment planning in interstitial HDR brachytherapy.

Patient specific distortion detection and mitigation in MR images used for stereotactic radiosurgery.

Objective.In MRI-based radiation therapy planning, mitigating patient-specific distortion with standard high bandwidth scans can result in unnecessary sacrifices of signal to noise ratio. This study investigates a technique for distortion detection and mitigation on a patient specific basis.Approach.Fast B0 mapping was performed using a previously developed technique for high-resolution, large dynamic range field mapping without the need for phase unwrapping algorithms. A phantom study was performed to validate the method. Distortion mitigation was validated by reducing geometric distortion with increased acquisition bandwidth and confirmed by both the B0 mapping technique and manual measurements. Images and contours from 25 brain stereotactic radiosurgery patients and 95 targets were analyzed to estimate the range of geometric distortions expected in the brain and to estimate bandwidth required to keep all treatment targets within the ±0.5 mm iso-distortion contour.Main Results.The phantom study showed, at 3 T, the technique can measure distortions with a mean absolute error of 0.12 mm (0.18 ppm), and a maximum error of 0.37 mm (0.6 ppm). For image acquisition at 3 T and 1.0 mm resolution, mean absolute distortion under 0.5 mm in patients required bandwidths from 109 to 200 Hz px-1for patients with the least and most distortion, respectively. Maximum absolute distortion under 0.5 mm required bandwidths from 120 to 390 Hz px-1.Significance.The method for B0 mapping was shown to be valid and may be applied to assess distortion clinically. Future work will adapt the readout bandwidth to prospectively mitigate distortion with the goal to improve radiosurgery treatment outcomes by reducing healthy tissue exposure.

Impact of personality on the cerebral processing of emotional prosody.

While several studies have focused on identifying common brain mechanisms governing the decoding of emotional speech melody, interindividual variations in the cerebral processing of prosodic information, in comparison, have received only little attention to date: Albeit, for instance, differences in personality among individuals have been shown to modulate emotional brain responses, personality influences on the neural basis of prosody decoding have not been investigated systematically yet. Thus, the present study aimed at delineating relationships between interindividual differences in personality and hemodynamic responses evoked by emotional speech melody. To determine personality-dependent modulations of brain reactivity, fMRI activation patterns during the processing of emotional speech cues were acquired from 24 healthy volunteers and subsequently correlated with individual trait measures of extraversion and neuroticism obtained for each participant. Whereas correlation analysis did not indicate any link between brain activation and extraversion, strong positive correlations between measures of neuroticism and hemodynamic responses of the right amygdala, the left postcentral gyrus as well as medial frontal structures including the right anterior cingulate cortex emerged, suggesting that brain mechanisms mediating the decoding of emotional speech melody may vary depending on differences in neuroticism among individuals. Observed trait-specific modulations are discussed in the light of processing biases as well as differences in emotion control or task strategies which may be associated with the personality trait of neuroticism.

Comparison of a 32-channel with a 12-channel head coil: are there relevant improvements for functional imaging?

PURPOSE: To evaluate the suitability of a 12- or 32-channel head coil and of a prescan normalization filter for functional magnetic resonance imaging (fMRI) studies at different brain regions. MATERIALS AND METHODS: fMRI was obtained from 36 volunteers executing a visually instructed motor paradigm using a 12-channel head matrix coil and a 32-channel phased-array head coil with and without prescan normalization filtering at 3 T. The time-course signal-to-noise ratio (tSNR) and the magnitude of functional activation (beta-value, t-value, percent signal change) were statistically compared between experimental conditions for the contralateral primary motor and visual cortex, contralateral thalamus, and ipsilateral anterior cerebellar hemispheres. RESULTS: tSNR was higher overall measuring with the 32-channel array and with prescan normalization. Without filtering, the 32-channel array delivered higher functional activation magnitudes for the visual cortex, whereas the 12-channel array seemed superior in this respect in thalamus and cerebellum. Filtering did not considerably affect the fMRI-activation magnitude detected from the 12-channel coil; its application favored the 32-channel coil at the subcortical and cerebellar locations but disfavored it at the cortical ones. CONCLUSION: The 32-channel coil detected more fMRI-activation cortically but less subcortically than the 12-channel coil; prescan normalization improved activation parameters only at central brain structures.

Feasibility of magnetic resonance-only high-dose-rate surface brachytherapy for clinical application.

PURPOSE: In this article, we investigate the feasibility of magnetic resonance (MR)-only imaging for high-dose-rate (HDR) surface brachytherapy (SABT). We examined whether a standard CT-based planning can be replaced with an MR-only planning. For this purpose, the MRI digitization and plan quality check processes were compared against the standard CT-based processes. A prospective clinical implementation of the MR-only planning was evaluated on a clinical data set. METHODS: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized for visualization of Freiburg flap (FF) on MR images. MR and conventional CT images were acquired with a FF applicator (Elekta, Stockholm, Sweden) placed on the following phantoms: (1) flat styrofoam (FST), FF locked-in placed with supporting structure; (2) cast-made facemask, and (3) porcine leg (PL). Catheters were digitized and activated with 10 mm step size on Oncentra Brachy 4.5.3 Treatment Planning System. The CT-only and MR-only treatment plans were generated by optimizing the dose to the target defined as volume at 3 mm skin depth. To compare the plans, the MRI-to-CT alignment was performed via rigid registration. Positional displacements of dwell positions between CT and MR plans were compared on the FST phantom and the relative percent dose difference in 2210 different points from CT or MR-only plans was compared. For all three phantoms, the comparabilities between CT and MR-only plans were assessed by calculating dice similarity coefficient (DSC) for volumes enclosing 150%, 125%, 100%, 95%, 90%, 80%, and 65% isodose lines (V150  -V65 ). The MR images of FF placed on the forearm of a healthy subject were acquired with this optimized PETRA sequence and used for treatment planning. The relative percent dose was calculated on 140 representative points placed at 3 mm skin depth to evaluate the dose to the skin. RESULTS: Using the optimized PETRA sequence, MRTP digitization accuracy was < 1 mm in each dimension and on three-dimensional (3D) displacement for the FST phantom. In each phantom and clinical data set, it was possible to generate MR-only treatment plans with the 3 mm skin depth prescription. In the FST phantom, the mean relative dose at the points was not significantly different (< 0.1% difference) for CT or MR-based plans. The assessment of similarities in dose profiles between CT and MR-only plans' provided DSC values greater than 0.96, 0.92, and 0.73 for all volumes enclosing up to 100%, 125%, and 150% isodose lines, respectively. CONCLUSION: The feasibility of generating a HDR treatment plan with FF using MR-only has been evaluated in phantoms with varying geometry and for a clinical data set. The optimization of a standard MRI sequence-PETRA-implemented in this study showed that FF-based catheters can be digitized and a plan can be generated using only MRI. The resulting MR-only plans were comparable to the conventional CT-based plans, suggesting that MRI alone can generate clinically acceptable plans for FF in phantoms and on a clinical data set. Reliable MR-only treatment planning could improve treatment prescription through more accurate characterization of soft tissue targets.

A review of the role of MRI in diagnosis and treatment of early stage lung cancer.

Despite magnetic resonance imaging (MRI) being a mainstay in the oncologic care for many disease sites, it has not routinely been used in early lung cancer diagnosis, staging, and treatment. While MRI provides improved soft tissue contrast compared to computed tomography (CT), an advantage in multiple organs, the physical properties of the lungs and mediastinum create unique challenges for lung MRI. Although multi-detector CT remains the gold standard for lung imaging, advances in MRI technology have led to its increased clinical relevance in evaluating early stage lung cancer. Even though positron emission tomography is used more frequently in this context, functional MR imaging, including diffusion-weighted MRI and dynamic contrast-enhanced MRI, are emerging as useful modalities for both diagnosis and evaluation of treatment response for lung cancer. In parallel with these advances, the development of combined MRI and linear accelerator devices (MR-linacs), has spurred the integration of MRI into radiation treatment delivery in the form of MR-guided radiotherapy (MRgRT). Despite challenges for MRgRT in early stage lung cancer radiotherapy, early data utilizing MR-linacs shows potential for the treatment of early lung cancer. In both diagnosis and treatment, MRI is a promising modality for imaging early lung cancer.

Reproducibility of the lung anatomy under active breathing coordinator control: Dosimetric consequences for scanned proton treatments.

PURPOSE: The treatment of moving targets with scanned proton beams is challenging. For motion mitigation, an Active Breathing Coordinator (ABC) can be used to assist breath-holding. The delivery of pencil beam scanning fields often exceeds feasible breath-hold durations, requiring high breath-hold reproducibility. We evaluated the robustness of scanned proton therapy against anatomical uncertainties when treating nonsmall-cell lung cancer (NSCLC) patients during ABC controlled breath-hold. METHODS: Four subsequent MRIs of five healthy volunteers (3 male, 2 female, age: 25-58, BMI: 19-29) were acquired under ABC controlled breath-hold during two simulated treatment fractions, providing both intrafractional and interfractional information about breath-hold reproducibility. Deformation vector fields between these MRIs were used to deform CTs of five NSCLC patients. Per patient, four or five cases with different tumor locations were modeled, simulating a total of 23 NSCLC patients. Robustly optimized (3 and 5 mm setup uncertainty respectively and 3% density perturbation) intensity-modulated proton plans (IMPT) were created and split into subplans of 20 s duration (assumed breath-hold duration). A fully fractionated treatment was recalculated on the deformed CTs. For each treatment fraction the deformed CTs representing multiple breath-hold geometries were alternated to simulate repeated ABC breath-holding during irradiation. Also a worst-case scenario was simulated by recalculating the complete treatment plan on the deformed CT scan showing the largest deviation with the first deformed CT scan, introducing a systematic error. Both the fractionated breath-hold scenario and worst-case scenario were dosimetrically evaluated. RESULTS: Looking at the deformation vector fields between the MRIs of the volunteers, up to 8 mm median intra- and interfraction displacements (without outliers) were found for all lung segments. The dosimetric evaluation showed a median difference in D98% between the planned and breath-hold scenarios of -0.1 Gy (range: -4.1 Gy to 2.0 Gy). D98% target coverage was more than 57.0 Gy for 22/23 cases. The D1 cc of the CTV increased for 21/23 simulations, with a median difference of 0.9 Gy (range: -0.3 to 4.6 Gy). For 14/23 simulations the increment was beyond the allowed maximum dose of 63.0 Gy, though remained under 66.0 Gy (110% of the prescribed dose of 60.0 Gy). Organs at risk doses differed little compared to the planned doses (difference in mean doses <0.9 Gy for the heart and lungs, <1.4% difference in V35 [%] and V20 [%] to the esophagus and lung). CONCLUSIONS: When treating under ABC controlled breath-hold, robustly optimized IMPT plans show limited dosimetric consequences due to anatomical variations between repeated ABC breath-holds for most cases. Thus, the combination of robustly optimized IMPT plans and the delivery under ABC controlled breath-hold presents a safe approach for PBS lung treatments.

A generalized framework unifying image registration and respiratory motion models and incorporating image reconstruction, for partial image data or full images.

Surrogate-driven respiratory motion models relate the motion of the internal anatomy to easily acquired respiratory surrogate signals, such as the motion of the skin surface. They are usually built by first using image registration to determine the motion from a number of dynamic images, and then fitting a correspondence model relating the motion to the surrogate signals. In this paper we present a generalized framework that unifies the image registration and correspondence model fitting into a single optimization. This allows the use of 'partial' imaging data, such as individual slices, projections, or k-space data, where it would not be possible to determine the motion from an individual frame of data. Motion compensated image reconstruction can also be incorporated using an iterative approach, so that both the motion and a motion-free image can be estimated from the partial image data. The framework has been applied to real 4DCT, Cine CT, multi-slice CT, and multi-slice MR data, as well as simulated datasets from a computer phantom. This includes the use of a super-resolution reconstruction method for the multi-slice MR data. Good results were obtained for all datasets, including quantitative results for the 4DCT and phantom datasets where the ground truth motion was known or could be estimated.

Automated detection of amyloid-ß-related cortical and subcortical signal changes in a transgenic model of Alzheimer's disease using high-field MRI.

In vivo imaging of amyloid-ß (Aß) load as a biomarker of Alzheimer's disease (AD) would be of considerable clinical relevance for the early diagnosis and monitoring of treatment effects. Here, we investigated automated quantification of in vivo T2 relaxation time as a surrogate measure of plaque load in the brains of ten AßPP/PS1 transgenic mice (age 20 weeks) using in vivo MRI acquisitions on a 7T Bruker ClinScan magnet. AßPP/PS1 mice present with rapid-onset cerebral ß-amyloidosis, and were compared with eight age-matched, wild-type control mice (C57Bl/6J) that do not develop Aß-deposition in brain. Data were analyzed with a novel automated voxel-based analysis that allowed mapping the entire brain for significant signal changes. In AßPP/PS1 mice, we found a significant decrease in T2 relaxation times in the deeper neocortical layers, caudate-putamen, thalamus, hippocampus, and cerebellum compared to wildtype controls. These changes were in line with the histological distribution of cerebral Aß plaques and activated microglia. Grey matter density did not differ between wild-type mice and AßPP/PS1 mice, consistent with a lack of neuronal loss in histological investigations. High-field MRI with automated mapping of T2 time changes may be a useful tool for the detection of plaque load in living transgenic animals, which may become relevant for the evaluation of amyloid lowering intervention effects in future studies.