Quantitative MRI assessment of joint effusion using T2-relaxometry at 3 Tesla: a feasibility and reproducibility study.

OBJECTIVE: T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia? MATERIALS AND METHODS: In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7 min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis. RESULTS: We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24 years; range 17-33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76-0.97; circular ROI: ICC = 0.82, 95% CI 0.66-0.91) and interobserver agreement was adequate (manual ROI: LoA = 71 ms; circular ROI: LoA = 146 ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI - 0.06-0.94; circular RO: ICC = 0.99, 95% CI 0.98-0.99) and intraobserver agreement was good (manual ROI: LoA = 63 ms; circular ROI: LoA = 41 ms). CONCLUSION: T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility.

Factors Influencing the Adoption of Magnetic Resonance-Guided High-Intensity Focused Ultrasound for Painful Bone Metastases in Europe, A Group Concept Mapping Study.

Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) is an innovative treatment for patients with painful bone metastases. The adoption of MR-HIFU will be influenced by several factors beyond its effectiveness. To identify contextual factors affecting the adoption of MR-HIFU, we conducted a group concept mapping (GCM) study in four European countries. The GCM was conducted in two phases. First, the participants brainstormed statements guided by the focus prompt "One factor that may influence the uptake of MR-HIFU in clinical practice is...". Second, the participants sorted statements into categories and rated the statements according to their importance and changeability. To generate a concept map, multidimensional scaling and cluster analysis were conducted, and average ratings for each (cluster of) factors were calculated. Forty-five participants contributed to phase I and/or II (56% overall participation rate). The resulting concept map comprises 49 factors, organized in 12 clusters: "competitive treatments", "physicians' attitudes", "alignment of resources", "logistics and workflow", "technical disadvantages", "radiotherapy as first-line therapy", "aggregating knowledge and improving awareness", "clinical effectiveness", "patients' preferences", "reimbursement", "cost-effectiveness" and "hospital costs". The factors identified echo those from the literature, but their relevance and interrelationship are case-specific. Besides evidence on clinical effectiveness, contextual factors from 10 other clusters should be addressed to support adoption of MR-HIFU.

Arterial spin labeling using spatio-temporal encoding readout for robust perfusion imaging in inhomogenous magnetic fields.

PURPOSE: To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. METHODS: A 2D self-refocused T2 *-compensated hybrid SPEN scheme, with super-resolution reconstruction was implemented on a 1.5T Philips system. Q (=BWchirp *Tchirp ) was varied and, the aneurysm clip-induced artifact was evaluated in phantom (label-images) as well as in vivo (perfusion-weighted signal (PWS)-maps and temporal SNR (tSNR)). In vivo results were compared to gradient-echo EPI (GE-EPI) and spin-echo EPI (SE-EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE-EPI. SPEN with Q Ëœ 75 encodes with the same off-resonance robustness as EPI. RESULTS: The clip-induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE-EPI and GE-EPI in vivo. tSNR decreased with Q and the tSNR of GE-EPI and SE-EPI corresponded to SPEN with a Q-value of approximately ˜85 and ˜108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p < 0.05) for TR = 4000 ms compared to TR = 2100 ms, while SE-EPI did not. tSNR remained relatively stable when the time between SPEN-excitation and start of the next labeling-module was more than ˜1000 ms. CONCLUSION: Feasibility of combining SPEN with pCASL imaging was demonstrated, enabling cerebral perfusion measurements with a higher robustness to field inhomogeneity (Q > 75) compared to SE-EPI and GE-EPI. However, the SPEN chirp-pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning.

Focused Ultrasound and RadioTHERapy for non-invasive palliative pain treatment in patients with bone metastasis: a study protocol for the three armed randomized controlled FURTHER trial.

BACKGROUND: Cancer-induced bone pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External beam radiotherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) may improve pain palliation in this patient population. The main objective of this trial was to compare MR-HIFU, EBRT, and MR-HIFU + EBRT for the palliative treatment of bone metastases. METHODS/DESIGN: The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of 6 months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL, and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after start of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day and at 4, 6, 12 and 24 weeks), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted. DISCUSSION: The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU-alone or in combination with EBRT-compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. TRIAL REGISTRATION: The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13-01-2020.

Early economic modeling of magnetic resonance image-guided high intensity focused ultrasound compared to radiotherapy for pain palliation of bone metastases.

Introduction: Magnetic Resonance Image-guided High Intensity Focused Ultrasound (MR-HIFU) is a non-invasive treatment option for palliative patients with painful bone metastases. Early evidence suggests that MR-HIFU is associated with similar overall treatment response, but more rapid pain palliation compared to external beam radiotherapy (EBRT). This modelling study aimed to assess the cost-effectiveness of MR-HIFU as an alternative treatment option for painful bone metastases from the perspective of the German Statutory Health Insurance (SHI). Materials and methods: A microsimulation model with lifelong time horizon and one-month cycle length was developed. To calculate the incremental cost-effectiveness ratio (ICER), strategy A (MR-HIFU as first-line treatment or as retreatment option in case of persistent pain or only partial pain relief after EBRT) was compared to strategy B (EBRT alone) for patients with bone metastases due to breast, prostate, or lung cancer. Input parameters used for the model were extracted from the literature. Results were expressed as EUR per quality-adjusted life years (QALYs) and EUR per pain response (i.e., months spent with complete or partial pain response). Deterministic and probabilistic sensitivity analyses (PSA) were performed to test the robustness of results, and a value of information analysis was conducted. Results: Compared to strategy B, strategy A resulted in additional costs (EUR 399) and benefits (0.02 QALYs and 0.95 months with pain response). In the base case, the resulting ICERs (strategy A vs. strategy B) are EUR 19,845/QALY and EUR 421 per pain response. Offering all patients MR-HIFU as first-line treatment would increase the ICER by 50% (31,048 EUR/QALY). PSA showed that at a (hypothetical) willingness to pay of EUR 20,000/QALY, the probability of MR-HIFU being cost-effective was 52%. The expected value of perfect information (EVPI) for the benefit population in Germany is approximately EUR 190 Mio. Conclusion: Although there is considerable uncertainty, the results demonstrate that introducing MR-HIFU as a treatment alternative for painful bone metastases might be cost-effective for the German SHI. The high EVPI indicate that further studies to reduce uncertainty would be worthwhile.

Ultrasound-directed enzyme-prodrug therapy (UDEPT) using self-immolative doxorubicin derivatives.

Background: Enzyme-activatable prodrugs are extensively employed in oncology and beyond. Because enzyme concentrations and their (sub)cellular compartmentalization are highly heterogeneous in different tumor types and patients, we propose ultrasound-directed enzyme-prodrug therapy (UDEPT) as a means to increase enzyme access and availability for prodrug activation locally. Methods: We synthesized ß-glucuronidase-sensitive self-immolative doxorubicin prodrugs with different spacer lengths between the active drug moiety and the capping group. We evaluated drug conversion, uptake and cytotoxicity in the presence and absence of the activating enzyme ß-glucuronidase. To trigger the cell release of ß-glucuronidase, we used high-intensity focused ultrasound to aid in the conversion of the prodrugs into their active counterparts. Results: More efficient enzymatic activation was observed for self-immolative prodrugs with more than one aromatic unit in the spacer. In the absence of ß-glucuronidase, the prodrugs showed significantly reduced cellular uptake and cytotoxicity compared to the parent drug. High-intensity focused ultrasound-induced mechanical destruction of cancer cells resulted in release of intact ß-glucuronidase, which activated the prodrugs, restored their cytotoxicity and induced immunogenic cell death. Conclusion: These findings shed new light on prodrug design and activation, and they contribute to novel UDEPT-based mechanochemical combination therapies for the treatment of cancer.

Synthetic CT for the planning of MR-HIFU treatment of bone metastases in pelvic and femoral bones: a feasibility study.

OBJECTIVES: Visualization of the bone distribution is an important prerequisite for MRI-guided high-intensity focused ultrasound (MRI-HIFU) treatment planning of bone metastases. In this context, we evaluated MRI-based synthetic CT (sCT) imaging for the visualization of cortical bone. METHODS: MR and CT images of nine patients with pelvic and femoral metastases were retrospectively analyzed in this study. The metastatic lesions were osteolytic, osteoblastic or mixed. sCT were generated from pre-treatment or treatment MR images using a UNet-like neural network. sCT was qualitatively and quantitatively compared to CT in the bone (pelvis or femur) containing the metastasis and in a region of interest placed on the metastasis itself, through mean absolute difference (MAD), mean difference (MD), Dice similarity coefficient (DSC), and root mean square surface distance (RMSD). RESULTS: The dataset consisted of 3 osteolytic, 4 osteoblastic and 2 mixed metastases. For most patients, the general morphology of the bone was well represented in the sCT images and osteolytic, osteoblastic and mixed lesions could be discriminated. Despite an average timespan between MR and CT acquisitions of 61 days, in bone, the average (± standard deviation) MAD was 116 ± 26 HU, MD - 14 ± 66 HU, DSC 0.85 ± 0.05, and RMSD 2.05 ± 0.48 mm and, in the lesion, MAD was 132 ± 62 HU, MD - 31 ± 106 HU, DSC 0.75 ± 0.2, and RMSD 2.73 ± 2.28 mm. CONCLUSIONS: Synthetic CT images adequately depicted the cancellous and cortical bone distribution in the different lesion types, which shows its potential for MRI-HIFU treatment planning. KEY POINTS: • Synthetic computed tomography was able to depict bone distribution in metastatic lesions. • Synthetic computed tomography images intrinsically aligned with treatment MR images may have the potential to facilitate MR-HIFU treatment planning of bone metastases, by combining visualization of soft tissues and cancellous and cortical bone.

Workflow for automatic renal perfusion quantification using ASL-MRI and machine learning.

PURPOSE: Clinical applicability of renal arterial spin labeling (ASL) MRI is hampered because of time consuming and observer dependent post-processing, including manual segmentation of the cortex to obtain cortical renal blood flow (RBF). Machine learning has proven its value in medical image segmentation, including the kidneys. This study presents a fully automatic workflow for renal cortex perfusion quantification by including machine learning-based segmentation. METHODS: Fully automatic workflow was achieved by construction of a cascade of 3 U-nets to replace manual segmentation in ASL quantification. All 1.5T ASL-MRI data, including M0 , T1 , and ASL label-control images, from 10 healthy volunteers was used for training (dataset 1). Trained cascade performance was validated on 4 additional volunteers (dataset 2). Manual segmentations were generated by 2 observers, yielding reference and second observer segmentations. To validate the intended use of the automatic segmentations, manual and automatic RBF values in mL/min/100 g were compared. RESULTS: Good agreement was found between automatic and manual segmentations on dataset 1 (dice score = 0.78 ± 0.04), which was in line with inter-observer variability (dice score = 0.77 ± 0.02). Good agreement was confirmed on dataset 2 (dice score = 0.75 ± 0.03). Moreover, similar cortical RBF was obtained with automatic or manual segmentations, on average and at subject level; with 211 ± 31 mL/min/100 g and 208 ± 31 mL/min/100 g (P < .05), respectively, with narrow limits of agreement at -11 and 4.6 mL/min/100 g. RBF accuracy with automated segmentations was confirmed on dataset 2. CONCLUSION: Our proposed method automates ASL quantification without compromising RBF accuracy. With quick processing and without observer dependence, renal ASL-MRI is more attractive for clinical application as well as for longitudinal and multi-center studies.

Perfusion imaging of neuroblastoma and nephroblastoma in a paediatric population using pseudo-continuous arterial spin-labelling magnetic resonance imaging.

OBJECTIVES: To examine the feasibility of performing ASL-MRI in paediatric patients with solid abdominal tumours. METHODS: Multi-delay ASL data sets were acquired in ten paediatric patients diagnosed with either a neuroblastoma (n = 4) or nephroblastoma (n = 6) during a diagnostic MRI examination at a single visit (n = 4 at initial staging, n = 2 neuroblastoma and n = 2 nephroblastoma patients; n = 6 during follow-up, n = 2 neuroblastoma and n = 4 nephroblastoma patients). Visual evaluation and region-of-interest (ROI) analyses were performed on the processed perfusion-weighted images to assess ASL perfusion signal dynamics in the whole tumour, contralateral kidney, and tumour sub-regions with/without contrast enhancement. RESULTS: The majority of the included abdominal tumours presented with relatively low perfusion-weighted signal (PWS), especially compared with the highly perfused kidneys. Within the tumours, regions with high PWS were observed which, at short PLD, are possibly related to labelled blood inside vessels and at long PLD, reflect labelled blood accumulating inside tumour tissue over time. Conversely, comparison of ASL perfusion-weighted image findings with T1w enhancement after contrast administration showed that regions lacking contrast enhancement also were void of PWS. DISCUSSION: This pilot study demonstrates the feasibility of utilizing ASL-MRI in paediatric patients with solid abdominal tumours and provides a basis for further research on non-invasive perfusion measurements in this study population.

Detecting low blood concentrations in joints using T1 and T2 mapping at 1.5, 3, and 7 T: an in vitro study.

BACKGROUND: Intra-articular blood causes irreversible joint damage, whilst clinical differentiation between haemorrhagic joint effusion and other effusions can be challenging. An accurate non-invasive method for the detection of joint bleeds is lacking. The aims of this phantom study were to investigate whether magnetic resonance imaging (MRI) T1 and T2 mapping allows for differentiation between simple and haemorrhagic joint effusion and to determine the lowest blood concentration that can be detected. METHODS: Solutions of synovial fluid with blood concentrations ranging from 0 to 100% were scanned at 1.5, 3, and 7 T. T1 maps were generated with an inversion recovery technique and T2 maps from multi spin-echo sequences. In both cases, the scan acquisition times were below 5 min. Regions of interest were manually drawn by two observers in the obtained T1 and T2 maps for each sample. The lowest detectable blood concentration was determined for all field strengths. RESULTS: At all field strengths, T1 and T2 relaxation times decreased with higher blood concentrations. The lowest detectable blood concentrations using T1 mapping were 10% at 1.5 T, 25% at 3 T, and 50% at 7 T. For T2 mapping, the detection limits were 50%, 5%, and 25%, respectively. CONCLUSIONS: T1 and T2 mapping can detect different blood concentrations in synovial fluid in vitro at clinical field strengths. Especially, T2 measurements at 3 T showed to be highly sensitive. Short acquisition times would make these methods suitable for clinical use and therefore might be promising tools for accurate discrimination between simple and haemorrhagic joint effusion in vivo.

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation.

Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultrasound system (Philips iU22) in combination with clinically approved microbubbles (SonoVue) leads to efficient in vitro sonopermeation. To this end, we measured the efficacy of USMB therapy for different US probes (S5-1, C5-1 and C9-4) and US parameters in FaDu cells. The US probe with the lowest central frequency (i.e. 1.6 MHz for S5-1) showed the highest USMB-induced intracellular uptake of the fluorescent dye SYTOX™ Green (SG). These SG uptake levels were comparable to or even higher than those obtained with a custom-built US system with optimized US parameters. Moreover, USMB therapy with both the clinical and the custom-built US system increased the cytotoxicity of the hydrophilic drug bleomycin. Our results demonstrate that a clinical US system can be used to perform USMB therapy as efficiently as a single-element transducer set-up with optimized US parameters. Therefore, future trials could be based on these clinical US systems, including validated US parameters, in order to accelerate successful translation of USMB therapy.

Feasibility of Velocity-Selective Arterial Spin Labeling in Breast Cancer Patients for Noncontrast-Enhanced Perfusion Imaging.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI is the most sensitive method for detection of breast cancer. However, due to high costs and retention of intravenously injected gadolinium-based contrast agent, screening with DCE-MRI is only recommended for patients who are at high risk for developing breast cancer. Thus, a noncontrast-enhanced alternative to DCE is desirable. PURPOSE: To investigate whether velocity selective arterial spin labeling (VS-ASL) can be used to identify increased perfusion and vascularity within breast lesions compared to surrounding tissue. STUDY TYPE: Prospective. POPULATION: Eight breast cancer patients. FIELD STRENGTH/SEQUENCE: A 3 T; VS-ASL with multislice single-shot gradient-echo echo-planar-imaging readout. ASSESSMENT: VS-ASL scans were independently assessed by three radiologists, with 3-25 years of experience in breast radiology. Scans were scored on lesion visibility and artifacts, based on a 3-point Likert scale. A score of 1 corresponded to "lesions being distinguishable from background" (lesion visibility), and "no or few artifacts visible, artifacts can be distinguished from blood signal" (artifact score). A distinction was made between mass and nonmass lesions (based on BI-RADS lexicon), as assessed in the standard clinical exam. STATISTICAL TESTS: Intra-class correlation coefficient (ICC) for interobserver agreement. RESULTS: The ICC was 0.77 for lesion visibility and 0.84 for the artifact score. Overall, mass lesions had a mean score of 1.27 on lesion visibility and 1.53 on the artifact score. Nonmass lesions had a mean score of 2.11 on lesion visibility and 2.11 on the artifact score. DATA CONCLUSION: We have demonstrated the technical feasibility of bilateral whole-breast perfusion imaging using VS-ASL in breast cancer patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Interleaved water and fat MR thermometry for monitoring high intensity focused ultrasound ablation of bone lesions.

PURPOSE: To demonstrate that interleaved MR thermometry can monitor temperature in water and fat with adequate temporal resolution. This is relevant for high intensity focused uUltrasounds (HIFU) treatment of bone lesions, which are often found near aqueous tissues, as muscle, or embedded in adipose tissues, as subcutaneous fat and bone marrow. METHODS: Proton resonance frequency shift (PRFS)-based thermometry scans and T1 -based 2D variable flip angle (2D-VFA) thermometry scans were acquired alternatingly over time. Temperature in water was monitored using PRFS thermometry, and in fat by 2D-VFA thermometry with slice profile effect correction. The feasibility of interleaved water/fat temperature monitoring was studied ex vivo in porcine bone during MR-HIFU sonication. Precision and stability of measurements in vivo were evaluated in a healthy volunteer under non-heating conditions. RESULTS: The method allowed observing temperature change over time in muscle and fat, including bone marrow, during MR-HIFU sonication, with a temporal resolution of 6.1 s. In vivo, the apparent temperature change was stable on the time scale of the experiment: In 7 min the systematic drift was <0.042°C/min in muscle (PRFS after drift correction) and <0.096°C/min in bone marrow (2D-VFA). The SD of the temperature change averaged over time was 0.98°C (PRFS) and 2.7°C (2D-VFA). CONCLUSIONS: Interleaved MR thermometry allows temperature measurements in water and fat with a temporal resolution high enough for monitoring HIFU ablation. Specifically, combined fat and water thermometry provides uninterrupted information on temperature changes in tissue close to the bone cortex.

Rapid 2D variable flip angle method for accurate and precise T1 measurements over a wide range of T1 values.

PURPOSE: To perform dynamic T1 mapping using a 2D variable flip angle (VFA) method, a correction for the slice profile effect is needed. In this work we investigated the impact of flip angle selection and excitation RF pulse profile on the performance of slice profile correction when applied to T1 mapping over a range of T1 values. METHODS: A correction of the slice profile effect is proposed, based on Bloch simulation of steady-state signals. With this correction, Monte Carlo simulations were performed to assess the accuracy and precision of 2D VFA T1 mapping in the presence of noise, for RF pulses with time-bandwidth products of 2, 3 and 10 and with flip angle pairs in the range [1°-90°]. To evaluate its performance over a wide range of T1 , maximum errors were calculated for six T1 values between 50 ms and 1250 ms. The method was demonstrated using in vitro and in vivo experiments. RESULTS: Without corrections, 2D VFA severely underestimates T1 . Slice profile errors were effectively reduced with the correction based on simulations, both in vitro and in vivo. The precision and accuracy of the method depend on the nominal T1 values, the FA pair, and the RF pulse shape. FA pairs leading to <5% errors in T1 can be identified for the common RF shapes, for T1 values between 50 ms and 1250 ms. CONCLUSIONS: 2D VFA T1 mapping with Bloch-simulation-based correction can deliver T1 estimates that are accurate and precise to within 5% over a wide T1 range.

Combining radiotherapy and focused ultrasound for pain palliation of cancer induced bone pain; a stage I/IIa study according to the IDEAL framework.

BACKGROUND: Cancer induced bone pain (CIBP) strongly interferes with patient's quality of life. Currently, the standard of care includes external beam radiotherapy (EBRT), resulting in pain relief in approximately 60% of patients. Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU) is a promising treatment modality for CIBP. METHODS: A single arm, R-IDEAL stage I/IIa study was conducted. Patients presenting at the department of radiation oncology with symptomatic bone metastases in the appendicular skeleton, as well as in the sacrum and sternum were eligible for inclusion. All participants underwent EBRT, followed by MR-HIFU within 4 days. Safety and feasibility were assessed, and pain scores were monitored for 4 weeks after completing the combined treatment. RESULTS: Six patients were enrolled. Median age was 67 years, median lesion diameter was 56,5 mm. In all patients it was logistically possible to plan and perform the MR-HIFU treatment within 4 days after EBRT. All patients tolerated the combined procedure well. Pain response was reported by 5 out of 6 patients at 7 days after completion of the combined treatment, and stabilized on 60% at 4 weeks follow up. No treatment related serious adverse events occurred. CONCLUSION: This is the first study to combine EBRT with MR-HIFU. Our results show that combined EBRT and MR-HIFU in first-line treatment of CIBP is safe and feasible, and is well tolerated by patients. Superiority over standard EBRT, in terms of (time to) pain relief and quality of life need to be evaluated in comparative (randomized) study.

Exploring label dynamics of velocity-selective arterial spin labeling in the kidney.

PURPOSE: Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR). METHODS: Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior-posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported. RESULTS: In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P < .05). Finally, the average cortical renal blood flow measured with cutoff velocities of 5 cm/s (398 ± 84 mL/min/100 g) and 10 cm/s (472 ± 160 mL/min/100 g) were similar to renal blood flow measured with FAIR (441 ± 84 mL/min/100 g) (P > .05) with good correlations on subject level. CONCLUSION: Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR.

Validation of multiparametric MRI by histopathology after nephrectomy: a case study.

OBJECTIVES: Renal multiparametric MRI (mpMRI) is a promising tool to monitor renal allograft health to enable timely treatment of chronic allograft nephropathy. This study aims to validate mpMRI by whole-kidney histology following transplantectomy. MATERIALS AND METHODS: A patient with kidney transplant failure underwent mpMRI prior to transplantectomy. The mpMRI included blood oxygenation level-dependent (BOLD) MRI, T1 and T2 mapping, diffusion-weighted imaging (DWI), 2D phase contrast (2DPC) and arterial spin labeling (ASL). Parenchymal mpMRI measures were compared to normative values obtained in 19 healthy controls. Differences were expressed in standard deviations (SD) of normative values. The mpMRI measures were compared qualitatively to histology. RESULTS: The mpMRI showed a heterogeneous parenchyma consistent with extensive interstitial hemorrhage on histology. A global increase in T1 (+ 3.0 SD) and restricted diffusivity (- 3.6 SD) were consistent with inflammation and fibrosis. Decreased T2 (- 1.8 SD) indicated fibrosis or hemorrhage. ASL showed diminished cortical perfusion (- 2.9 SD) with patent proximal arteries. 2DPC revealed a 69% decrease in renal perfusion. Histological evaluation showed a dense inflammatory infiltrate and fibrotic changes, consistent with mpMRI results. Most interlobular arteries were obliterated while proximal arteries were patent, consistent with ASL findings. DISCUSSION: mpMRI findings correlated well with histology both globally as well as locally.

Multiparametric Renal MRI: An Intrasubject Test-Retest Repeatability Study.

BACKGROUND: Renal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease. PURPOSE: To determine intrasubject test-retest repeatability of renal MRI measurements. STUDY TYPE: Prospective. POPULATION: Nineteen healthy subjects aged over 40 years. FIELD STRENGTH/SEQUENCES: T1 and T2 mapping, R2 * mapping or blood oxygenation level-dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T. ASSESSMENT: Subjects were scanned twice with ~1 week between visits. Total scan time was ~1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model. STATISTICAL TEST: To assess the repeatability, a Bland-Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated. RESULTS: CoVs for relaxometry (T1 , T2 , R2 */BOLD) were below 6.1%, with the lowest CoVs for T2 maps and highest for R2 */BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP ), with CoVs ranging from 18-24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7-87% (lowest/highest values for medullary mean diffusivity and cortical FP , respectively) and intraclass correlation coefficients (ICCs) ranged from -0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively). DATA CONCLUSION: CoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Multi-organ comparison of flow-based arterial spin labeling techniques: Spatially non-selective labeling for cerebral and renal perfusion imaging.

PURPOSE: Flow-based arterial spin labeling (ASL) techniques provide a transit-time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow-based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow-dynamics, field-inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow-based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI-ASL]) to the current spatially selective reference techniques in brain (ie, pseudo-continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]). METHODS: Brain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion-weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced-breathing and free-breathing (kidney). RESULTS: In brain, all flow-based ASL techniques showed similar tSNR as pCASL, but only VSI-ASL showed similar sensitivity to perfusion changes. In kidney, all flow-based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI-ASL showed a sensitivity to B1 -inhomogeneity. All ASL techniques were relatively robust to respiratory motion. CONCLUSION: In both brain and kidney, flow-based ASL techniques provide a planning-free and transit-time insensitive alternative to spatially selective ASL techniques. VSI-ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B1 -sensitivity of VSI-ASL is necessary to match the performance of FAIR.