High-Resolution Magnetic Resonance Neurography at 7T: A Pilot Study of Hand Innervation.

The emergence of 7T clinical MRI technology has sparked our interest in its ability to discern the complex structures of the hand. Our primary objective was to assess the sensory and motor nerve structures of the hand, specifically nerves and Pacinian corpuscles, with the dual purpose of aiding diagnostic endeavors and supporting reconstructive surgical procedures. Ethical approval was obtained to carry out 7T MRI scans on a cohort of volunteers. Four volunteers assumed a prone position, with their hands (N = 8) positioned in a "superman" posture. To immobilize and maintain the hand in a strictly horizontal position, it was affixed to a plastic plate. Passive B0 shimming was implemented. Once high-resolution 3D images had been acquired using a multi-transmit head coil, advanced post-processing techniques were used to meticulously delineate the nerve fiber networks and mechanoreceptors. Across all participants, digital nerves were consistently located on the phalanges area, on average, between 2.5 and 3.5 mm beneath the skin, except within flexion folds where the nerve was approximately 1.8 mm from the surface. On the phalanges area, the mean distance from digital nerves to joints was approximately 1.5 mm. The nerves of the fingers were closer to the bone than to the surface of the skin. Furthermore, Pacinian corpuscles exhibited a notable clustering primarily within the metacarpal zone, situated on the palmar aspect. Our study yielded promising results, successfully reconstructing and meticulously describing the anatomy of nerve fibers spanning from the carpus to the digital nerve division, alongside the identification of Pacinian corpuscles, in four healthy volunteers (eight hands).

Hand Dystonia after Focused Ultrasound Thalamotomy in Essential Tremor.

INTRODUCTION: Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait disturbance, paresthesias, dysgeusia, and hemiparesis. Here, we report the first case of thalamic hand dystonia rapidly occurring after MRgFUS thalamotomy of the ventral intermediate nucleus (V.im). CASE PRESENTATION: MRgFUS thalamotomy was performed in a 60-year-old left-handed patient for his disabling medically refractory essential tremor. The intervention resulted in a marked reduction of his action tremor. However, the patient developed an unvoluntary abnormal posture in his left hand a few days after the procedure with difficulty holding a cigarette between his fingers. Brain MRI revealed the expected MRgFUS lesion within the right V.im as well as an extension of the lesion anteriorly to the V.im in the ventro-oralis nucleus. Tractography showed that the lesion disrupted the dentato-rubro-thalamic tract as expected with a lesion suppressing tremor. However, the lesion also was interrupted fibers connecting to the superior frontal and pre-central cortices (primary motor cortex, premotor cortex, and supplementary area). We hypothesized that the interventional MRgFUS thalamotomy was slightly off target, which induced a dysfunction within the cortico-striato-thalamo-cortical network and the cerebello-thalamo-cortical pathway reaching a sufficient threshold of basal ganglia/cerebellum circuitry interference to induce dystonia. CONCLUSION: This rare side effect emphasizes the risk of imbalance within the dystonia network (i.e., basal ganglia-cerebello-thalamo-cortical circuit) secondary to V.im thalamotomy.

Successful MRI-Guided Focused Ultrasound Thalamotomy after Ipsilateral Gamma Knife Radiosurgery for Essential Tremor: A Case Report with Video.

We report the case of a 67-year-old left-handed female patient with disabling medically refractory essential tremor who underwent successful right-sided magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus after ipsilateral gamma knife radiosurgery (GKRS) thalamotomy performed 3 years earlier. The GKRS had a partial effect on her postural tremor without side effects, but there was no reduction of her kinetic tremor or improvement in her quality of life (QoL). The patient subsequently underwent a MRgFUS thalamotomy, which induced an immediate and marked reduction in both the postural and kinetic tremor components, with minor complications (left upper lip hypesthesia, dysmetria in her left hand, and slight gait ataxia). The MRgFUS-induced lesion was centered more medially than the GKRS-induced lesion and extended more posteriorly and inferiorly. The MRgFUS-induced lesion interrupted remaining fibers of the dentatorubrothalamic tract (DRTT). The functional improvement 1-year post-MRgFUS was significant due to a marked reduction of the patient's kinetic tremor. The QoL score (Quality of Life in Essential Tremor) improved by 88% and her Clinical Rating Scale for Tremor left hand score by 62%. The side effects persisted but were minor, with no impact on her QoL. The explanation for the superior efficacy of MRgFUS compared to GKRS in our patient could be due to either a poor response to the GKRS or to a better localization of the MRgFUS lesion with a more extensive interruption of DRTT fibers. In conclusion, MRgFUS can be a valuable therapeutic option after unsatisfactory GKRS, especially because MRgFUS has immediate clinical effectiveness, allowing intra-procedural test lesions and possible readjustment of the target if necessary.

Clinical outcomes of 3T magnetic resonance imaging-guided lumbar and sacral foraminal injections.

PURPOSE: This article evaluates the feasibility, safety, and efficacy of MRI-guided lumbar or sacral nerve root infiltration for chronic back pain. We compared the outcomes of our MRI-guided infiltrations with data from CT-guided infiltrations reported in the literature and explored the potential advantages of MRI guidance. METHOD: Forty-eight MRI-guided nerve root infiltrations were performed using a 3 T MRI machine. The optimal needle path was determined using breathhold T2-weighted sequences, and the needle was advanced under interleaved guidance based on breathhold PD-weighted images. Pain levels were assessed using a numeric rating scale (NRS) before the procedure and up to 5 months after, during follow-up. Procedure success was evaluated by comparing patients' pain levels before and after the infiltration. RESULTS: The MRI-guided infiltrations yielded pain reduction 1 week after the infiltration in 92% of cases, with an average NRS substantial change of 3.9 points. Pain reduction persisted after 5 months for 51% of procedures. No procedure-related complications occurred. The use of a 22G needle and reconstructed subtraction images from T2 FatSat sequences improved the workflow. CONCLUSION: Our study showed that MRI-guided nerve root infiltration is a feasible, safe, and effective treatment option for chronic back pain. Precise positioning of the needle tip and accurate distribution of the injected solution contributed to the effectiveness of MRI-guided infiltration, which appeared to be as accurate as CT-guided procedures. Further research is needed to explore the potential benefits of metal artifact reduction sequences to optimize chronic back pain management.

In Vivo Thermal Ablation of Deep Intrahepatic Targets Using a Super-Convergent MRgHIFU Applicator and a Pseudo-Tumor Model.

BACKGROUND: HIFU ablation of liver malignancies is particularly challenging due to respiratory motion, high tissue perfusion and the presence of the rib cage. Based on our previous development of a super-convergent phased-array transducer, we aimed to further investigate, in vivo, its applicability to deep intrahepatic targets. METHODS: In a series of six pigs, a pseudo-tumor model was used as target, visible both on intra-operatory MRI and post-mortem gross pathology. The transcostal MRgHIFU ablation was prescribed coplanar with the pseudo-tumor, either axial or sagittal, but deliberately shifted 7 to 18 mm to the side. No specific means of protection of the ribs were implemented. Post-treatment MRI follow-up was performed at D7, followed by animal necropsy and gross pathology of the liver. RESULTS: The pseudo-tumor was clearly identified on T1w MR imaging and subsequently allowed the MRgHIFU planning. The peak temperature at the focal point ranged from 58-87 °C. Gross pathology confirmed the presence of the pseudo-tumor and the well-delineated MRgHIFU ablation at the expected locations. CONCLUSIONS: The specific design of the transducer enabled a reliable workflow. It demonstrated a good safety profile for in vivo transcostal MRgHIFU ablation of deep-liver targets, graded as challenging for standard surgery.

Assessing Enhanced Acoustic Absorption From Sonosensitive Perfluorocarbon Emulsion With Magnetic Resonance-Guided High-Intensity Focused Ultrasound and a Percolated Tissue-Mimicking Flow Phantom.

OBJECTIVE: Sonosensitive high-boiling point perfluorocarbon F8TAC18-PFOB emulsions previously exhibited thermal enhancement during focused ultrasound heating in ex vivo pig livers, kidneys and a laminar flow phantom. The main objectives of this study were to evaluate heating under turbulent conditions, observe perfusion effects, quantify heating in terms of acoustic absorption and model the experimental data. METHODS: In this study, similar perfluorocarbon emulsions were circulated at incremental concentrations of 0.07, 0.13, 0.19 and 0.25% v:v through a percolated turbulent flow phantom, more representative of the biological tissue than a laminar flow phantom. The concentrations represent the droplet content in only the perfused fluid, rather than the droplet concentration throughout the entire cross-section. The temperature was measured with magnetic resonance thermometry, during focused ultrasound sonications of 67 W, 95% duty cycle and 33 s duration. These were used in Bioheat equation simulations to investigate in silico the thermal phenomena. The temperature change was compared with the control condition by circulating de-gassed and de-ionized water through the flow phantom without droplets. RESULTS: With these 1.24 µm diameter droplets at 0.25% v:v, the acoustic absorption coefficient increased from 0.93 ± 0.05 at 0.0% v:v to 1.82 ± 0.22 m-1 at 0.25% v:v using a 0.1 mL s-1 flow rate. Without perfusion at 0.25% v:v, an increase was observed from 1.23 ± 0.07 m-1 at 0.0% v:v to 1.65 ± 0.17 m-1. CONCLUSION: The results further support previously reported thermal enhancement with F8TAC18-PFOB emulsion, quantified the increased absorption at small concentration intervals, illustrated that the effects can be observed in a variety of visceral tissue models and provided a method to simulate untested scenarios.

A tailored passive driver for liver MRE in pediatric patients.

Objectives: Magnetic resonance elastography (MRE) is increasingly used in the pediatric population for diagnosis and staging of liver fibrosis. However, the MR-compatible driver and sequences are usually those used for adult patients. Our feasibility study aimed to adapt the standardized adult MRE passive driver and vibrational parameters to a pediatric population. Methods: We designed an elliptic passive driver shaped on a torus equipped with an elastic membrane and adapted to children's morphologies. As a first step, eight children (aged 8-18 years) were enrolled in a prospective pilot study aiming to determine the threshold vibrational amplitude for MRE using a custom passive driver, based on phase aliasing assessment and the occurrence of signal void artifacts on magnitude MR images. In the second step, the practicality and the consistency of the custom driver were assessed in a further 11 pediatric patients (aged 7-18 years). In the third step, we compared our custom driver vs. the commercial driver on six adult volunteers, in terms of the reliable region of interest area within the acquired MRE slices, the shear wave maps' quality, and measured stiffness values obtained. Results: Based on pediatric patient data, the threshold vibrational amplitude expressed as percentage of maximum output was found to be 0.4 and 1.1 times the body weight (kg) at 40 and 60 Hz frequencies, respectively. In comparison to the commercial passive driver, the custom driver improved threefold the contact with the body surface, also enabling a more comfortable examination as self-assessed by the volunteers. Conclusions: Our custom driver was more comfortable for the volunteers and was able to generate more homogenous shear waves, yielding larger usable hepatic area, and more reliable stiffness values.

A Novel Concept of a Phased-Array HIFU Transducer Optimized for MR-Guided Hepatic Ablation: Embodiment and First In-Vivo Studies.

Purpose: High-intensity focused ultrasound (HIFU) is challenging in the liver due to the respiratory motion and risks of near-/far-field burns, particularly on the ribs. We implemented a novel design of a HIFU phased-array transducer, dedicated to transcostal hepatic thermo-ablation. Due to its large acoustic window and strong focusing, the transducer should perform safely for this application. Material and Methods: The new HIFU transducer is composed of 256 elements distributed on 5 concentric segments of a specific radius (either 100, 111, or 125 mm). It has been optimally shaped to fit the abdominal wall. The shape and size of the acoustic elements were optimized for the largest emitting surface and the lowest symmetry. Calibration tests have been conducted on tissue-mimicking gels under 3-T magnetic resonance (MR) guidance. In-vivo MR-guided HIFU treatment was conducted in two pigs, aiming to create thermal ablation deep in the liver without significant side effects. Imaging follow-up was performed at D0 and D7. Sacrifice and post-mortem macroscopic examination occurred at D7, with the ablated tissue being fixed for pathology. Results: The device showed -3-dB focusing capacities in a volume of 27 × 46 × 50 mm3 as compared with the numerical simulation volume of 18 × 48 × 60 mm3. The shape of the focal area was in millimeter-range agreement with the numerical simulations. No interference was detected between the HIFU sonication and the MR acquisition. In vivo, the temperature elevation in perivascular liver parenchyma reached 28°C above physiological temperature, within one breath-hold. The lesion was visible on Gd contrast-enhanced MRI sequences and post-mortem examination. The non-perfused volume was found in pig #1 and pig #2 of 8/11, 6/8, and 7/7 mm along the LR, AP, and HF directions, respectively. No rib burns or other near-field side effects were visually observed on post-mortem gross examination. High-resolution contrast-enhanced 3D MRI indicated a minor lesion on the sternum. Conclusion: The performance of this new HIFU transducer has been demonstrated in vitro and in vivo. The transducer meets the requirement to perform thermal lesions in deep tissues, without the need for rib-sparing means.

Diffusion-Weighted MRI in the Genitourinary System.

Diffusion weighted imaging (DWI) constitutes a major functional parameter performed in Magnetic Resonance Imaging (MRI). The DW sequence is performed by acquiring a set of native images described by their b-values, each b-value representing the strength of the diffusion MR gradients specific to that sequence. By fitting the data with models describing the motion of water in tissue, an apparent diffusion coefficient (ADC) map is built and allows the assessment of water mobility inside the tissue. The high cellularity of tumors restricts the water diffusion and decreases the value of ADC within tumors, which makes them appear hypointense on ADC maps. The role of this sequence now largely exceeds its first clinical apparitions in neuroimaging, whereby the method helped diagnose the early phases of cerebral ischemic stroke. The applications extend to whole-body imaging for both neoplastic and non-neoplastic diseases. This review emphasizes the integration of DWI in the genitourinary system imaging by outlining the sequence's usage in female pelvis, prostate, bladder, penis, testis and kidney MRI. In gynecologic imaging, DWI is an essential sequence for the characterization of cervix tumors and endometrial carcinomas, as well as to differentiate between leiomyosarcoma and benign leiomyoma of the uterus. In ovarian epithelial neoplasms, DWI provides key information for the characterization of solid components in heterogeneous complex ovarian masses. In prostate imaging, DWI became an essential part of multi-parametric Magnetic Resonance Imaging (mpMRI) to detect prostate cancer. The Prostate Imaging-Reporting and Data System (PI-RADS) scoring the probability of significant prostate tumors has significantly contributed to this success. Its contribution has established mpMRI as a mandatory examination for the planning of prostate biopsies and radical prostatectomy. Following a similar approach, DWI was included in multiparametric protocols for the bladder and the testis. In renal imaging, DWI is not able to robustly differentiate between malignant and benign renal tumors but may be helpful to characterize tumor subtypes, including clear-cell and non-clear-cell renal carcinomas or low-fat angiomyolipomas. One of the most promising developments of renal DWI is the estimation of renal fibrosis in chronic kidney disease (CKD) patients. In conclusion, DWI constitutes a major advancement in genitourinary imaging with a central role in decision algorithms in the female pelvis and prostate cancer, now allowing promising applications in renal imaging or in the bladder and testicular mpMRI.

Synthetic 4DCT(MRI) lung phantom generation for 4D radiotherapy and image guidance investigations.

PURPOSE: Respiratory motion is one of the major challenges in radiotherapy. In this work, a comprehensive and clinically plausible set of 4D numerical phantoms, together with their corresponding "ground truths," have been developed and validated for 4D radiotherapy applications. METHODS: The phantoms are based on CTs providing density information and motion from multi-breathing-cycle 4D Magnetic Resonance imagings (MRIs). Deformable image registration (DIR) has been utilized to extract motion fields from 4DMRIs and to establish inter-subject correspondence by registering binary lung masks between Computer Tomography (CT) and MRI. The established correspondence is then used to warp the CT according to the 4DMRI motion. The resulting synthetic 4DCTs are called 4DCT(MRI)s. Validation of the 4DCT(MRI) workflow was conducted by directly comparing conventional 4DCTs to derived synthetic 4D images using the motion of the 4DCTs themselves (referred to as 4DCT(CT)s). Digitally reconstructed radiographs (DRRs) as well as 4D pencil beam scanned (PBS) proton dose calculations were used for validation. RESULTS: Based on the CT image appearance of 13 lung cancer patients and deformable motion of five volunteer 4DMRIs, synthetic 4DCT(MRI)s with a total of 871 different breathing cycles have been generated. The 4DCT(MRI)s exhibit an average superior-inferior tumor motion amplitude of 7 ± 5 mm (min: 0.5 mm, max: 22.7 mm). The relative change of the DRR image intensities of the conventional 4DCTs and the corresponding synthetic 4DCT(CT)s inside the body is smaller than 5% for at least 81% of the pixels for all studied cases. Comparison of 4D dose distributions calculated on 4DCTs and the synthetic 4DCT(CT)s using the same motion achieved similar dose distributions with an average 2%/2 mm gamma pass rate of 90.8% (min: 77.8%, max: 97.2%). CONCLUSION: We developed a series of numerical 4D lung phantoms based on real imaging and motion data, which give realistic representations of both anatomy and motion scenarios and the accessible "ground truth" deformation vector fields of each 4DCT(MRI). The open-source code and motion data allow foreseen users to generate further 4D data by themselves. These numeric 4D phantoms can be used for the development of new 4D treatment strategies, 4D dose calculations, DIR algorithm validations, as well as simulations of motion mitigation and different online image guidance techniques for both proton and photon radiation therapy.

Combined hyperthermia and radiotherapy for prostate cancer: a systematic review.

Optimization of treatment strategies for prostate cancer patients treated with curative radiation therapy (RT) represents one of the major challenges for the radiation oncologist. Dose escalation or combination of RT with systemic therapies is used to improve tumor control in patients with unfavorable prostate cancer, at the risk of increasing rates and severity of treatment-related toxicities. Elevation of temperature to a supra-physiological level has been shown to both increase tumor oxygenation and reduce DNA repair capabilities. Thus, hyperthermia (HT) combined with RT represents a compelling treatment strategy to improve the therapeutic ratio in prostate cancer patients. The aim of the present systematic review is to report on preclinical and clinical evidence supporting the combination of HT and RT for prostate cancer, discussing future applications and developments of this combined treatment.

PFOB sonosensitive microdroplets: determining their interaction radii with focused ultrasound using MR thermometry and a Gaussian convolution kernel computation.

Purpose: Micron-sized perfluorocarbon droplet adjuvants to focused ultrasound therapies allow lower applied power, circumvent unwanted prefocal heating, and enhance thermal dose in highly perfused tissues. The heat enhancement has been shown to saturate at increasing concentrations. Experiments were performed to empirically model the saturating heating effects during focused ultrasound.Materials and methods: The measurements were made at varying concentrations using magnetic resonance thermometry and focused ultrasound by circulating droplets of mean diameter 1.9 to 2.3 µm through a perfused phantom. A simulation was performed to estimate the interaction radius size, empirically.Results: The interaction radius, representing the radius of a sphere encompassing 90% of the probability for the transformation of acoustic energy into heat deposition around a single droplet, was determined experimentally from ultrasonic absorption coefficient measurements The simulations suggest the interaction radius was approximately 12.5-fold larger than the geometrical radius of droplets, corresponding to an interaction volume on the order of 2000 larger than the geometrical volume.Conclusions: The results provide information regarding the dose-response relationship from the droplets, a measure with 15% precision of their interaction radii with focused ultrasound, and subsequent insights into the underlying physical heating mechanism.

Perfluorocarbon emulsion enhances MR-ARFI displacement and temperature in vitro: Evaluating the response with MRI, NMR, and hydrophone.

Sonosensitive perfluorocarbon F8TAC18-PFOB emulsion is under development to enhance heating, increase thermal contrast, and reduce treatment times during focused ultrasound tumor ablation of highly perfused tissue. The emulsion previously showed enhanced heating during ex vivo and in vitro studies. Experiments were designed to observe the response in additional scenarios by varying focused ultrasound conditions, emulsion concentrations, and surfactants. Most notably, changes in acoustic absorption were assessed with MR-ARFI. Phantoms were developed to have thermal, elastic, and relaxometry properties similar to those of ex vivo pig tissue. The phantoms were embedded with varying amounts of F8TAC18-PFOB emulsion or lecithin-PFOB emulsion, between about 0.0-0.3% v:w, in 0.05% v:w increments. MR-ARFI measurements were performed using a FLASH-ARFI-MRT sequence to obtain simultaneous displacement and temperature measurements. A Fabry-Perot hydrophone was utilized to observe the acoustic emissions. Susceptibility-weighted imaging and relaxometry mapping were performed to observe concentration-dependent effects. 19F diffusion-ordered spectroscopy NMR was used to measure the diffusion coefficient of perfluorocarbon droplets in a water emulsion. Increased displacement and temperature were observed with higher emulsion concentration. In semi-rigid MR-ARFI phantoms, a linear response was observed with low-duty cycle MR-ARFI sonications and a mono-exponential saturating response was observed with sustained sonications. The emulsifiers did not have a significant effect on acoustic absorption in semi-rigid gels. Stable cavitation might also contribute to enhanced heating.

A Novel Concept of Transperineal Focused Ultrasound Transducer for Prostate Cancer Local Deep Hyperthermia Treatments.

Design, embodiment, and experimental study of a novel concept of extracorporeal phased array ultrasound transducer for prostate cancer regional deep hyperthermia treatments using a transperineal acoustic window is presented. An optimized design of hyperthermia applicator was derived from a modelling software where acoustic and thermal fields were computed based on anatomical data. Performance tests have been experimentally conducted on gel phantoms and tissues, under 3T MRI guidance using PRFS thermometry. Feedback controlled hyperthermia (ΔT = 5 °C during 20min) was performed on two ex vivo lamb carcasses with prostate mimicking pelvic tissue, to demonstrate capability of spatio-temporal temperature control and to assess potential risks and side effects. Our optimization approach yielded a therapeutic ultrasound transducer consisting of 192 elements of variable shape and surface, pseudo randomly distributed on 6 columns, using a frequency of 700 kHz. Radius of curvature was 140 mm and active water circulation was included for cooling. The measured focusing capabilities covered a volume of 24 × 50 × 60 mm3. Acoustic coupling of excellent quality was achieved. No interference was detected between sonication and MR acquisitions. On ex vivo experiments the target temperature elevation of 5 °C was reached after 5 min and maintained during another 15 min with the predictive temperature controller showing 0.2 °C accuracy. No significant temperature rise was observed on skin and bonny structures. Reported results represent a promising step toward the implementation of transperineal ultrasound hyperthermia in a pilot study of reirradiation in prostate cancer patients.

Magnetic resonance imaging-guided lumbar nerve root infiltrations: optimization of an in-house protocol.

BACKGROUND: For the treatment of radicular pain, nerve root infiltrations can be performed under MRI guidance in select, typically younger, patients where repeated CT exams are not desirable due to associated radiation risk, or potential allergic reactions to iodinated contrast medium. METHODS: Fifteen 3 T MRI-guided nerve root infiltrations were performed in 12 patients with a dedicated surface coil combined with the standard spine coil, using a breathhold PD sequence. The needle artifact on the MR images and the distance between the needle tip and the infiltrated nerve root were measured. RESULTS: The distance between the needle tip and the nerve root was 2.1 ± 1.4 mm. The visual artifact width, perpendicular to the needle long axis, was 2.1 ± 0.7 mm. No adverse events were reported. CONCLUSION: This technical note describes the optimization of the procedure in a 3 T magnetic field, including reported procedure time and an assessment of targeting precision.

Identification of hippocampal cortical microinfarcts on postmortem 3-T magnetic resonance imaging.

Cortical microinfarcts (CMI) are increasingly recognized in the neurological community as a biomarker related to cognitive impairment and dementia. If their radiological depiction has been largely described in experimental settings using ultra-high-field magnetic resonance imaging (MRI), less is known about their visibility on routinely used 3-T MRI. In this radiologic-pathologic correlation study, using 3-T post-mortem MRI, we searched for hippocampal CMI, in a double-blinded fashion, and found that only 4/36, or 11%, were clearly demonstrated on both radiological and histopathological exams.

Perfluorocarbon Emulsion Contrast Agents: A Mini Review.

Perfluorocarbon emulsions offer a variety of applications in medical imaging. The substances can be useful for most radiological imaging modalities; including, magnetic resonance imaging, ultrasonography, computed tomography, and positron emission tomography. Recently, the substance has gained much interest for theranostics, with both imaging and therapeutic potential. As MRI sequences improve and more widespread access to 19F-MRI coils become available, perfluorocarbon emulsions have great potential for new commercial imaging agents, due to high fluorine content and previous regulatory approval as antihypoxants and blood substitutes. This mini review aims to discuss the chemistry and physics of these contrast agents, in addition to highlighting some of the past, recent, and potential applications.

Liver-ultrasound-guided lung tumour tracking for scanned proton therapy: a feasibility study.

Pencil beam scanned (PBS) proton therapy of lung tumours is hampered by respiratory motion and the motion-induced density changes along the beam path. In this simulation study, we aim to investigate the effectiveness of proton beam tracking for lung tumours both under ideal conditions and in conjunction with a respiratory motion model guided by real-time ultrasound imaging of the liver. Multiple-breathing-cycle 4DMRIs of the thorax and abdominal 2D ultrasound images were acquired simultaneously for five volunteers. Deformation vector fields extracted from the 4DMRI, referred to as ground truth motion, were used to generate 4DCT(MRI) data sets of two lung cancer patients, resulting in 10 data sets with variable motion patterns. Given the 4DCT(MRI) and the corresponding ultrasound images as surrogate data, a patient-specific motion model was built. The model consists of an autoregressive model and Gaussian process regression for the temporal and spatial prediction, respectively. Two-field PBS plans were optimised on the reference CTs, and 4D dose calculations (4DDC) were used to simulate dose delivery for (a) unmitigated motion, (b) ideal 2D and 3D tracking (both beam adaption and 4DDC based on ground truth motion), and (c) realistic 2D and 3D tracking (beam adaption based on motion predictions, 4DDC on ground truth motion). Model-guided tracking retrieved clinically acceptable target dose homogeneity, as seen in a substantial reduction of the D5%-D95% compared to the non-mitigated simulation. Tracking in 2D and 3D resulted in a similar improvement of the dose homogeneity, as did ideal and realistic tracking simulations. In some cases, however, the tracked deliveries resulted in a shift towards higher or lower dose levels, leading to unacceptable target over- or under-coverage. The presented motion modelling framework was shown to be an accurate motion prediction tool for the use in proton beam tracking. Tracking alone, however, may not always effectively mitigate motion effects, making it necessary to combine it with other techniques such as rescanning.

Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers.

BACKGROUND: High intensity focused ultrasound (HIFU) is clinically accepted for the treatment of solid tumors but remains challenging in highly perfused tissue due to the heat sink effect. Endovascular liquid-core sonosensitizers have been previously suggested to enhance the thermal energy deposition at the focal area and to lower the near-/far-field heating. We are investigating the therapeutic potential of PFOB-FTAC micro-droplets in a perfused tissue-mimicking model and postmortem excised organs. METHOD: A custom-made in vitro perfused tissue-mimicking model, freshly excised pig kidneys (n = 3) and liver (n = 1) were perfused and subjected to focused ultrasound generated by an MR-compatible HIFU transducer. PFOB-FTAC sonosensitizers were injected in the perfusion fluid up to 0.235% v/v ratio. Targeting and on-line PRFS thermometry were performed on a 3 T MR scanner. Assessment of the fluid perfusion was performed with pulsed color Doppler in vitro and with dynamic contrast-enhanced (DCE)-MRI in excised organs. RESULTS: Our in vitro model of perfused tissue demonstrated re-usability. Sonosensitizer concentration and perfusion rate were tunable in situ. Differential heating under equivalent HIFU sonications demonstrated a dramatic improvement in the thermal deposition due to the sonosensitizers activity. Typically, the energy deposition was multiplied by a factor between 2.5 and 3 in perfused organs after the administration of micro-droplets, while DCE-MRI indicated an effective perfusion. CONCLUSION: The current PFOB-FTAC micro-droplet sonosensitizers provided a large and sustained enhancement of the HIFU thermal deposition at the focal area, suggesting solutions for less technological constraints, lower risk for the near-/far- field heating. We also report a suitable experimental model for other MRgHIFU studies.

Liver-ultrasound based motion modelling to estimate 4D dose distributions for lung tumours in scanned proton therapy.

Motion mitigation strategies are crucial for scanned particle therapy of mobile tumours in order to prevent geometrical target miss and interplay effects. We developed a patient-specific respiratory motion model based on simultaneously acquired time-resolved volumetric MRI and 2D abdominal ultrasound images. We present its effects on 4D pencil beam scanned treatment planning and simulated dose distributions. Given an ultrasound image of the liver and the diaphragm, principal component analysis and Gaussian process regression were applied to infer dense motion information of the lungs. 4D dose calculations for scanned proton therapy were performed using the estimated and the corresponding ground truth respiratory motion; the differences were compared by dose difference volume metrics. We performed this simulation study on 10 combined CT and 4DMRI data sets where the motion characteristics were extracted from 5 healthy volunteers and fused with the anatomical CT data of two lung cancer patients. Median geometrical estimation errors below 2 mm for all data sets and maximum dose differences of [Formula: see text] = 43.2% and [Formula: see text] = 16.3% were found. Moreover, it was shown that abdominal ultrasound imaging allows to monitor organ drift. This study demonstrated the feasibility of the proposed ultrasound-based motion modelling approach for its application in scanned proton therapy of lung tumours.