Phantom and in vivo accuracy of frameless optical navigation in stereotactic laser interstitial thermal therapy.

OBJECTIVE: Targeting accuracy presents a key factor in achieving maximal safe ablation in laser interstitial thermal therapy (LITT). The VarioGuide system has proven precise for brain biopsies, but data showing its accuracy in combination with LITT are limited. The aim of this study was to determine the phantom and in vivo accuracy of LITT probe placement using the VarioGuide system and to evaluate the effect of targeting error on maximum possible ablation volume. METHODS: Stereotactic LITT probe placement was performed using the VarioGuide system in 3 phantom skulls. The same system was used in 10 patients treated with LITT, for which data were retrospectively analyzed. Target point error (TPE), target depth deviation (TDD), target lateral deviation (TLD), and angular deviation (AD) were derived from intraprocedural MRI scans of both the phantom and in vivo trajectories. In vivo, the effect of targeting error on the maximum reachable ablation was calculated as the difference between the planned maximal achievable tumor ablation (PTA) and the actual maximal achievable tumor ablation (ATA). RESULTS: In total, 24 phantom and 16 in vivo trajectories were analyzed. In the phantom setting, the median TPE was 3.3 mm and median AD was 1.9°. Targeting accuracy significantly decreased for longer trajectories and those less perpendicular to the skull. In patients, the authors observed a comparable median TPE of 4.0 mm but significantly higher AD of 3.2°. In vivo, targeting inaccuracy resulted in a median decrease in maximum achievable ablation volume of 6% as compared to the planned trajectory. CONCLUSIONS: The authors' study indicates that utilizing the VarioGuide system in combination with LITT yields an average targeting error as large as 4 mm, which was smaller for shorter and straighter trajectories. In patients, targeting inaccuracy resulted in a median 6% decrease of the planned tumor ablation volume. These are important factors that should be considered in optimal case planning and patient selection in LITT.

MRI-Guided Salvage Focal Cryoablation: A 10-Year Single-Center Experience in 114 Patients with Localized Recurrent Prostate Cancer.

Patients with localized recurrent prostate cancer (PCa) are eligible for androgen-deprivation therapy, salvage radical prostatectomy (RP) or radiation therapy. These treatments are associated with serious side-effects, illustrating the need for alternative local treatment options with lower morbidity rates. All patients who underwent magnetic resonance imaging (MRI)-guided salvage focal cryoablation (SFC) with localized recurrent PCa between 2011-2021 (n = 114) were included. Two subgroups were formed: patients without (n = 99) and with prior RP (n = 15). We assessed the recurrence- (RFS) and treatment-free survival (TFS), measured from date of treatment to date of recurrence or initiation of additional salvage treatment, using Kaplan-Meier plots. Complications were reported using the Clavien-Dindo (CD) scale. Overall 1-year and 5-year RFS were 76.0% and 25.1%, and overall 1-year and 5-year TFS were 91.5% and 58.2%, respectively. Patients without prior RP showed a significantly higher 1-year (78.5% vs. 52.5%) and 5-year RFS (28.1% vs. 0.0%; p = 0.03), and a trend towards a higher 1-year (92.6% vs. 79.0%) and 5-year TFS (60.2% vs. 23.0%; p = 0.10) compared to those with prior RP. A total of 46 complications occurred in 37 patients, and the overall complication rate was 32.4% (37/114 patients). The majority (41/46; 89.1%) of complications were minor (CD 1-2). Overall (31.3 vs. 40.0%) and major (3.0 vs. 13.3%) complication rates were lower in patients without compared to those with prior RP, respectively. MRI-guided SFC is an effective and safe therapy for patients with recurrent PCa, and has proved to delay and potentially prevent the initiation of salvage treatments. Patients with locally recurrent PCa after prior RP had an increased risk of recurrence, a shortened time to additional treatment, and more complications compared to those without prior RP, which should be considered when selecting patients for SFC.

Study protocol for a multicenter randomised controlled trial on the (cost)effectiveness of biopsy combined with same-session MR-guided LITT versus biopsy alone in patients with primary irresectable glioblastoma (EMITT trial).

BACKGROUND: Glioblastoma (GBM) is the most common primary, malignant brain tumour with a 5-year survival of 5%. If possible, a glioblastoma is resected and further treated with chemoradiation therapy (CRT), but resection is not feasible in about 30% of cases. Current standard of care in these cases is a biopsy followed by CRT. Magnetic resonance (MR) imaging-guided laser interstitial thermal therapy (LITT) has been suggested as a minimally invasive alternative when surgery is not feasible. However, high-quality evidence directly comparing LITT with standard of care is lacking, precluding any conclusions on (cost-)effectiveness. We therefore propose a multicenter randomized controlled study to assess the (cost-)effectiveness of MR-guided LITT as compared to current standard of care (EMITT trial). METHODS AND ANALYSIS: The EMITT trial will be a multicenter pragmatic randomized controlled trial in the Netherlands. Seven Dutch hospitals will participate in this study. In total 238 patients will be randomized with 1:1 allocation to receive either biopsy combined with same-session MR-guided LITT therapy followed by CRT or the current standard of care being biopsy followed by CRT. The primary outcomes will be health-related quality of life (HR-QoL) (non-inferiority) using EORTC QLQ-C30 + BN20 scores at 5 months after randomization and overall survival (superiority). Secondary outcomes comprise cost-effectiveness (healthcare and societal perspective) and HR-QoL of life over an 18-month time horizon, progression free survival, tumour response, disease specific survival, longitudinal effects, effects on adjuvant treatment, ablation percentage and complication rates. DISCUSSION: The EMITT trial will be the first RCT on the effectiveness of LITT in patients with glioblastoma as compared with current standard of care. Together with the Dutch Brain Tumour Patient association, we hypothesize that LITT may improve overall survival without substantially affecting patients' quality of life. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05318612).

MR-guided LITT therapy in patients with primary irresectable glioblastoma: a prospective, controlled pilot study.

PURPOSE: Laser interstitial thermal therapy (LITT) is increasingly being used in the treatment of brain tumors, whereas high-quality evidence of its effectiveness is lacking. This pilot examined the feasibility of conducting a randomized controlled trial (RCT) in patients with irresectable newly diagnosed glioblastoma (nGBM), and generated data on technical feasibility and safety. METHODS: We included patients with irresectable nGBM with KPS ≥ 70 and feasible trajectories to ablate ≥ 70% of the tumor volume. Patients were initially randomized to receive either biopsy combined with LITT or biopsy alone, followed by chemoradiation (CRT). Randomization was stopped after 9 patients as the feasibility endpoint with respect to willingness to be randomized was met. Main endpoints were feasibility of performing an RCT, technical feasibility of LITT and safety. Follow-up was 3 months. RESULTS: A total of 15 patients were included, of which 10 patients received a biopsy followed by LITT and 5 patients a biopsy. Most patients were able to complete the follow-up procedures (93% clinical, 86% questionnaires, 78% MRI). Patients were planned within 3 weeks after consultation (median 12 days, range 8-16) and no delay was observed in referring patients for CRT (median 37 days, range 28-61). Two CD ≥ 3 complications occurred in the LITT arm and none in the biopsy arm. CONCLUSION: An RCT to study the effectiveness of LITT in patients with an irresectable nGBM seems feasible with acceptable initial safety data. The findings from this pilot study helped to further refine the design of a larger full-scale multicenter RCT in the Netherlands. Protocol and study identifier: The current study is registered at clinicaltrials.gov (EMITT pilot study, NTR: NCT04596930).

Stereotactic laser ablation in neuro-oncology - A survey among European neurosurgeons.

Introduction: In the last decades, the application of stereotactic laser ablation (SLA) for the treatment of intracranial tumours has been growing, even though comparative trials are lacking. Our aim was to investigate the familiarity with SLA of neurosurgeons in Europe and their opinion regarding potential neuro-oncological indications. Furthermore, we investigated treatment preferences and variability for three exemplar neuro-oncological cases and willingness to refer for SLA. Material and methods: A 26-questions survey was mailed to members of the EANS neuro-oncology section. We presented three clinical cases of respectively deep-seated glioblastoma, recurrent metastasis and recurrent glioblastoma. Descriptive statistics was applied to report results. Results: 110 respondents completed all questions. Recurrent glioblastoma and recurrent metastases were regarded as the most feasible indications for SLA (chosen by 69% and 58% of the respondents) followed by newly diagnosed high-grade gliomas (31%). Seventy percent of respondents would refer patients for SLA. The majority of respondents would consider SLA as a treatment option for all three presented cases: 79% for the deep-seated glioblastoma case, 65% for the recurrent metastasis case and 76% for the recurrent glioblastoma case. Among respondents who wouldn't consider SLA, preference for standard treatment and lack of clinical evidence were reported as the main reasons. Conclusions: Most of respondents considered SLA as a treatment option for recurrent glioblastoma, recurrent metastases and newly diagnosed deep-seated glioblastoma. At the moment the current evidence to support such a treatment is very low. Comparative prospective trials are needed to support the use of SLA and determine proper indications.

Intraoperative MRI-derived volumetric ablation margins and initial correlation with local outcome after MRI-guided cryoablation of renal tumors.

PURPOSE: To assess volumetric ablation margins derived from intraoperative pre- and post-ablation MRI after magnetic resonance imaging (MRI)-guided percutaneous cryoablation of renal tumors and explore its correlation with local treatment success. METHODS: Retrospective analysis was performed on 30 patients (mean age 69y) who underwent percutaneous MRI-guided cryoablation between May 2014 and May 2020 for 32 renal tumors (size: 1.6-5.1 cm). Tumor and ice-ball volumes were segmented on intraprocedural pre- and post-ablation MR images using Software Assistant for Interventional Radiology (SAFIR) software. After MRI-MRI co-registration, the software automatically quantified the minimal treatment margin (MTM),defined as the smallest 3D distance between the tumor and ice-ball surface. Local tumor progression (LTP) after cryoablation was assessed on follow-up imaging. RESULTS: Median follow-up was 16 months (range: 1-58). Local control after cryoablation was achieved in 26 cases (81%) while LTP occurred in 6 (19%). The intended MTM of ≥5 mm was achieved in 3/32 (9%) cases. Median MTM was significantly smaller for cases with (- 7 mm; IQR:-10 to - 5) vs. without LTP (3 mm; IQR:2 to 4) (P < .001). All cases of LTP had a negative MTM. All negative treatment margins occurred in tumors > 3 cm. CONCLUSIONS: Determination of volumetric ablation margins from intraoperative MRI was feasible and may be useful in predicting local outcome after MRI-guided renal cryoablation. In our preliminary data, an intraoperative MRI-derived minimal margin extending at least 1 mm beyond the MRI-visible tumor led to local control and this was more difficult to achieve in tumors > 3 cm. Ultimately, online margin analysis may be a valuable tool to intraoperatively assess therapy success, but larger prospective studies are needed to establish a reliable threshold for clinical use.

The Influence of Irreversible Electroporation Parameters on the Size of the Ablation Zone and Thermal Effects: A Systematic Review.

Introduction: The aim of this study was to review the effect of irreversible electroporation parameter settings on the size of the ablation zone and the occurrence of thermal effects. This insight would help to optimize treatment protocols and effectively ablate a tumor while controlling the occurrence of thermal effects. Methods: Various individual studies report the influence of variation in electroporation parameters on the ablation zone size or occurrence of thermal effects. However, no connections have yet been established between these studies. With the aim of closing the gap in the understanding of and personalizing irreversible electroporation parameter settings, a systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A quality assessment was performed using an in-house developed grading tool based on components of commonly used grading domains. Data on the electroporation parameters voltage, number of electrodes, inter-electrode distance, active needle length, pulse length/number/protocol/frequency, and pulse interval were extracted. Ablation zone size and temperature data were grouped per parameter. Spearman correlation and linear regression were used to define the correlation with outcome measures. Results: A total of 7661 articles were screened, of which 18 preclinical studies (animal and phantom studies) met the inclusion criteria. These studies were graded as moderate (4/18) and low (14/18) quality. Only the applied voltage appeared to be a significant linear predictor of ablation zone size: length, surface, and volume. The pulse number was moderately but nonlinearly correlated with the ablation zone length. Thermal effects were more likely to occur for higher voltages (≥2000 V), higher number of electrodes, and increased active needle length. Conclusion: Firm conclusions are limited since studies that investigated and precisely reported the influence of electroporation parameters on the ablation zone size and thermal effects were scarce and mostly graded low quality. High-quality studies are needed to improve the predictability of the combined effect of variation in parameter combinations and optimize irreversible electroporation treatment protocols.

Improving MRI-based dosimetry for holmium-166 transarterial radioembolization using a nonrigid image registration for voxelwise Δ R 2 ∗ $\Delta R_2

BACKGROUND: Transarterial radioembolization (TARE) is a treatment modality for liver tumors during which radioactive microspheres are injected into the hepatic arterial system. These microspheres distribute throughout the liver as a result of the blood flow until they are trapped in the arterioles because of their size. Holmium-166 (166 Ho)-loaded microspheres used for TARE can be visualized and quantified with MRI, as holmium is a paramagnetic metal and locally increases the transverse relaxation rate R 2 ∗ $R_2^*$ . The current 166 Ho quantification method does not take regional differences in baseline R 2 ∗ $R_2^*$ values (such as between tumors and healthy tissue) into account, which intrinsically results in a systematic error in the estimated absorbed dose distribution. As this estimated absorbed dose distribution can be used to predict response to treatment of tumors and potential toxicity in healthy tissue, a high accuracy of absorbed dose estimation is required. PURPOSE: To evaluate pre-existing differences in R 2 ∗ $R_2^*$ distributions between tumor tissue and healthy tissue and assess the feasibility and accuracy of voxelwise subtraction-based Δ R 2 ∗ $\Delta R_2^*$ calculation for MRI-based dosimetry of holmium-166 transarterial radioembolization (166 Ho TARE). METHODS: MRI data obtained in six patients who underwent 166 Ho TARE of the liver as part of a clinical study was retrospectively evaluated. Pretreatment differences in R 2 ∗ $R_2^*$ distributions between tumor tissue and healthy tissue were characterized. Same-day pre- and post-treatment R 2 ∗ $R_2^*$ maps were aligned using a deformable registration algorithm and subsequently subtracted to generate voxelwise Δ R 2 ∗ $\Delta R_2^*$ maps and resultant absorbed dose maps. Image registration accuracy was quantified using the dice similarity coefficient (DSC), relative overlay (RO), and surface dice (≤4 mm; SDSC). Voxelwise subtraction-based absorbed dose maps were quantitatively (root-mean-square error, RMSE) and visually compared to the current MRI-based mean subtraction method and routinely used SPECT-based dosimetry. RESULTS: Pretreatment R 2 ∗ $R_2^*$ values were lower in tumors than in healthy liver tissue (mean 36.8 s-1 vs. 55.7 s-1 , P = 0.004). Image registration improved the mean DSC of 0.83 (range: 0.70-0.88) to 0.95 (range: 0.92-0.97), mean RO of 0.71 (range 0.53-0.78) to 0.90 (range: 0.86-0.94), and mean SDSC ≤4 mm of 0.47 (range: 0.28-0.67) to 0.97 (range: 0.96-0.98). Voxelwise subtraction-based absorbed dose maps yielded a higher tumor-absorbed dose (median increase of 9.0%) and lower healthy liver-absorbed dose (median decrease of 13.8%) compared to the mean subtraction method. Voxelwise subtraction-based absorbed dose maps corresponded better to SPECT-based absorbed dose maps, reflected by a lower RMSE in three of six patients. CONCLUSIONS: Voxelwise subtraction presents a robust alternative method for MRI-based dosimetry of 166 Ho microspheres that accounts for pre-existing R 2 ∗ $R_2^*$ differences, and appears to correspond better with SPECT-based dosimetry compared to the currently implemented mean subtraction method.

Intraprocedural MRI-based dosimetry during transarterial radioembolization of liver tumours with holmium-166 microspheres (EMERITUS-1): a phase I trial towards adaptive, image-controlled treatment delivery.

PURPOSE: Transarterial radioembolization (TARE) is a treatment for liver tumours based on injection of radioactive microspheres in the hepatic arterial system. It is crucial to achieve a maximum tumour dose for an optimal treatment response, while minimizing healthy liver dose to prevent toxicity. There is, however, no intraprocedural feedback on the dose distribution, as nuclear imaging can only be performed after treatment. As holmium-166 (166Ho) microspheres can be quantified with MRI, we investigate the feasibility and safety of performing 166Ho TARE within an MRI scanner and explore the potential of intraprocedural MRI-based dosimetry. METHODS: Six patients were treated with 166Ho TARE in a hybrid operating room. Per injection position, a microcatheter was placed under angiography guidance, after which patients were transported to an adjacent 3-T MRI system. After MRI confirmation of unchanged catheter location, 166Ho microspheres were injected in four fractions, consisting of 10%, 30%, 30% and 30% of the planned activity, alternated with holmium-sensitive MRI acquisition to assess the microsphere distribution. After the procedures, MRI-based dose maps were calculated from each intraprocedural image series using a dedicated dosimetry software package for 166Ho TARE. RESULTS: Administration of 166Ho microspheres within the MRI scanner was feasible in 9/11 (82%) injection positions. Intraprocedural holmium-sensitive MRI allowed for tumour dosimetry in 18/19 (95%) of treated tumours. Two CTCAE grade 3-4 toxicities were observed, and no adverse events were attributed to treatment in the MRI. Towards the last fraction, 4/18 tumours exhibited signs of saturation, while in 14/18 tumours, the microsphere uptake patterns did not deviate from the linear trend. CONCLUSION: This study demonstrated feasibility and preliminary safety of a first in-human application of TARE within a clinical MRI system. Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE. This proof of concept yields unique possibilities to better understand microsphere distribution in vivo and to potentially optimize treatment efficacy through treatment personalization. REGISTRATION: Clinicaltrials.gov, identifier NCT04269499, registered on February 13, 2020 (retrospectively registered).

Current State of MRI-Guided Endovascular Arterial Interventions: A Systematic Review of Preclinical and Clinical Studies.

BACKGROUND: MRI guidance of arterial endovascular interventions could be beneficial as it does not require radiation exposure, allows intrinsic blood-tissue contrast, and enables three-dimensional and functional imaging, however, clinical applications are still limited. PURPOSE: To review the current state of MRI-guided arterial endovascular interventions and to identify the most commonly reported challenges. STUDY TYPE: Systematic review. POPULATION: Pubmed, Embase, Web of Science, and The Cochrane Library were systematically searched to find relevant articles. The search strategy combined synonyms for vascular pathology, endovascular therapy, and real-time MRI guidance. FIELD STRENGTH/SEQUENCE: No field strength or sequence restrictions were applied. ASSESSMENT: Two reviewers independently identified and reviewed the original articles and extracted relevant data. STATISTICAL TESTS: Results of the included original articles are reported. RESULTS: A total of 24,809 studies were identified for screening. Eighty-eight studies were assessed for eligibility, after which data were extracted from 43 articles (6 phantom, 33 animal, and 4 human studies). Reported technical success rates for animal and human studies ranged between 42% to 100%, and the average complication rate was 5.8% (animal studies) and 8.8% (human studies). Main identified challenges were related to spatial and temporal resolution as well as safety, design, and scarcity of current MRI-compatible endovascular devices. DATA CONCLUSION: MRI guidance of endovascular arterial interventions seems feasible, however, included articles included mostly small single-center case series. Several hurdles remain to be overcome before larger trials can be undertaken. Main areas of research should focus on adequate imaging protocols with integrated tracking of dedicated endovascular devices.

Study Protocol PROMETHEUS: Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma.

PURPOSE: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of < 10% in patients with hepatocellular carcinoma undergoing thermal ablation. Secondary objectives are to analyze the correlation between ablation margins and local recurrence and to assess efficacy. MATERIALS AND METHODS: This study is a prospective, multicenter, non-experimental, non-comparative, open-label study. Patients > 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan-Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. DISCUSSION: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713 .

Optimised passive marker device visibility and automatic marker detection for 3-T MRI-guided endovascular interventions: a pulsatile flow phantom study.

BACKGROUND: Passive paramagnetic markers on magnetic resonance imaging (MRI)-compatible endovascular devices induce susceptibility artifacts, enabling MRI-visibility and real-time MRI-guidance. Optimised visibility is crucial for automatic detection and device tracking but depends on MRI technical parameters and marker characteristics. We assessed marker visibility and automatic detection robustness for varying MRI parameters and marker characteristics in a pulsatile flow phantom. METHODS: Guidewires with varying iron(II,III) oxide nanoparticle (IONP) concentration markers were imaged using gradient-echo (GRE) and balanced steady-state free precession (bSSFP) sequences at 3 T. Furthermore, echo time (TE), slice thickness (ST) and phase encoding direction (PED) were varied. Artifact width was measured and contrast-to-noise ratios were calculated. Marker visibility and image quality were scored by two MRI interventional radiologists. Additionally, a deep learning model for automatic marker detection was trained and the effects of the parameters on detection performance were evaluated. Two-tailed Wilcoxon signed-rank tests were used (significance level, p < 0.05). RESULTS: Medan artifact width (IQR) was larger in bSSFP compared to GRE images (12.7 mm (11.0-15.2) versus 8.4 mm (6.5-11.0)) (p < 0.001) and showed a positive relation with TE and IONP concentration. Switching PED and doubling ST had limited effect on artifact width. Image quality assessment scores were higher for GRE compared to bSSFP images. The deep learning model automatically detected the markers. However, the model performance was reduced after adjusting PED, TE, and IONP concentration. CONCLUSION: Marker visibility was sufficient and a large range of artifact sizes was generated by adjusting TE and IONP concentration. Deep learning-based marker detection was feasible but performance decreased for altered MR parameters. These factors should be considered to optimise device visibility and ensure reliable automatic marker detectability in MRI-guided endovascular interventions.

Safety aspects of the PiCCO thermodilution-cardiac output catheter during magnetic resonance imaging at 3 Tesla.

Thermodilution cardiac output monitoring, using a thermistor-tipped intravascular catheter, is used in critically ill patients to guide hemodynamic therapy. Often, these patients also need magnetic resonance imaging (MRI) for diagnostic or prognostic reasons. As thermodilution catheters contain metal, they are considered MRI-unsafe and advised to be removed prior to investigation. However, removal and replacement of the catheter carries risks of bleeding, perforation and infection. This research is an in vitro safety assessment of the PiCCO™ thermodilution catheter during 3 T Magnetic Resonance Imaging (3T-MRI).  In a 3T-MRI environment, three different PiCCO™ catheter sizes were investigated in an agarose-gel, tissue mimicking phantom. Two temperature probes measured radiofrequency-induced heating; one at the catheter tip and one at a reference point. Magnetically induced catheter dislocation was assessed by visual observation as well as by analysis of the tomographic images. For all tested catheters, the highest measured temperature increase was 0.2 °C at the center of the bore and 0.3 °C under "worst-case" setting for the tested MRI pulse sequences. No magnetically induced catheter displacements were observed. Under the tested circumstances, no heating or dislocation of the PiCCO™ catheter was observed in a tissue mimicking phantom during 3T-MRI. Leaving the catheter in the critically ill patient during MRI investigation might pose a lower risk of complications than catheter removal and replacement.

Development of an MRI-Guided Approach to Selective Internal Radiation Therapy Using Holmium-166 Microspheres.

Selective internal radiation therapy (SIRT) is a treatment modality for liver tumours during which radioactive microspheres are injected into the hepatic arterial tree. Holmium-166 (166Ho) microspheres used for SIRT can be visualized and quantified with MRI, potentially allowing for MRI guidance during SIRT. The purpose of this study was to investigate the MRI compatibility of two angiography catheters and a microcatheter typically used for SIRT, and to explore the detectability of 166Ho microspheres in a flow phantom using near real-time MRI. MR safety tests were performed at a 3 T MRI system according to American Society for Testing of Materials standard test methods. To assess the near real-time detectability of 166Ho microspheres, a flow phantom was placed in the MRI bore and perfused using a peristaltic pump, simulating the flow in the hepatic artery. Dynamic MR imaging was performed using a 2D FLASH sequence during injection of different concentrations of 166Ho microspheres. In the safety assessment, no significant heating (ΔTmax 0.7 °C) was found in any catheter, and no magnetic interaction was found in two out of three of the used catheters. Near real-time MRI visualization of 166Ho microsphere administration was feasible and depended on holmium concentration and vascular flow speed. Finally, we demonstrate preliminary imaging examples on the in vivo catheter visibility and near real-time imaging during 166Ho microsphere administration in an initial patient case treated with SIRT in a clinical 3 T MRI. These results support additional research to establish the feasibility and safety of this procedure in vivo and enable the further development of a personalized MRI-guided approach to SIRT.

To 1000 Gy and back again: a systematic review on dose-response evaluation in selective internal radiation therapy for primary and secondary liver cancer.

PURPOSE: To systematically review all current evidence into the dose-response relation of yttrium-90 and holmium-166 selective internal radiation therapy (SIRT) in primary and secondary liver cancer. METHODS: A standardized search was performed in PubMed (MEDLINE), Embase, and the Cochrane Library in order to identify all published articles on dose-response evaluation in SIRT. In order to limit the results, all articles that investigated SIRT in combination with other therapy modalities (such as chemotherapy) were excluded. RESULTS: A total of 3038 records were identified of which 487 were screened based on the full text. Ultimately, 37 studies were included for narrative analysis. Meta-analysis could not be performed due to the large heterogeneity in study and reporting designs. Out of 37 studies, 30 reported a 'mean dose threshold' that needs to be achieved in order to expect a response. This threshold appears to be higher for hepatocellular carcinoma (HCC, 100-250 Gy) than for colorectal cancer metastases (CRC, 40-60 Gy). Reported thresholds tend to be lower for resin microspheres than when glass microspheres are used. CONCLUSION: Although the existing evidence demonstrates a dose-response relationship in SIRT for both primary liver tumours and liver metastases, many pieces of the puzzle are still missing, hampering the definition of standardized dose thresholds. Nonetheless, most current evidence points towards a target mean dose of 100-250 Gy for HCC and 40-60 Gy for CRC. The field would greatly benefit from a reporting standard and prospective studies designed to elucidate the dose-response relation in different tumour types.

Laser Interstitial Thermal Therapy in Patients with Newly Diagnosed Glioblastoma: A Systematic Review.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimal invasive neurosurgical technique for the treatment of brain tumors. Results of LITT have been reported in a case series of patients with deep seated and/or recurrent glioblastoma or cerebral metastases. With this review we aim to summarize the currently available evidence regarding safety and effectiveness of LITT in patients with newly diagnosed glioblastoma (nGBM). METHODS: A literature search was performed using electronic databases (PubMed and Embase). Papers were assessed for the methodological quality using the Risk Of Bias In Non- randomised Studies - of Interventions (ROBINS-I) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the quality of the evidence. RESULTS: We identified 835 papers of which only 11 articles were eligible for our review. All papers suffered from serious or critical risk of bias, and the quality of evidence was graded as very low according to the GRADE criteria. None of the studies was randomized and reporting of confounders and other parameters was poor. Median overall survival (OS) ranged from 4.1 to 32 months and progression free survival (PFS) from 2 to 31 months. The mean complication rate was 33.7%. No quality of life or cost-effectiveness data were reported. CONCLUSIONS: Due to the low quality of the studies, it is not possible to draw firm conclusions regarding the (cost) effectiveness of LITT in patients with newly diagnosed glioblastoma. The low quality of evidence shows the need for a well-designed prospective multicenter randomized controlled trial.

Effect of irreversible electroporation parameters and the presence of a metal stent on the electric field line pattern.

The final ablation zone created with irreversible electroporation (IRE) depends on the size, shape and strength of the electric field that is influenced by several parameters. A profound understanding of the effect of IRE parameter alterations on the electric field are a prerequisite for a safe and effective treatment. Here, we demonstrate a semolina in castor oil model that enables visualization of the static electric field developed by a high-voltage generator between two needle-electrodes. We intuitively visualize the variation in electric field line pattern for selected IRE parameters; active needle length, inter-needle distance, applied voltage and presence of a nearby metal stent, by cameras in three dimensions. The observations were compared to and supported by two-dimensional numerical simulations of the electric field. Our semolina model visualizes the disturbance of the electric field by a metal stent, potentially leading to an incomplete tumour ablation between the needles. The reduction in electric field strength and the area at risk for incomplete tumour ablation are confirmed by the numerical simulations. The semolina model provides insight in the fundamental physics of the electric field, the effect of alterations in IRE parameter combinations and presence of a metal stent within the ablation zone.

Definitions of Computer-Assisted Surgery and Intervention, Image-Guided Surgery and Intervention, Hybrid Operating Room, and Guidance Systems: Strasbourg International Consensus Study.

OBJECTIVE: To develop consensus definitions of image-guided surgery, computer-assisted surgery, hybrid operating room, and surgical navigation systems. SUMMARY BACKGROUND DATA: The use of minimally invasive procedures has increased tremendously over the past 2 decades, but terminology related to image-guided minimally invasive procedures has not been standardized, which is a barrier to clear communication. METHODS: Experts in image-guided techniques and specialized engineers were invited to engage in a systematic process to develop consensus definitions of the key terms listed above. The process was designed following review of common consensus-development methodologies and included participation in 4 online surveys and a post-surveys face-to-face panel meeting held in Strasbourg, France. RESULTS: The experts settled on the terms computer-assisted surgery and intervention, image-guided surgery and intervention, hybrid operating room, and guidance systems and agreed-upon definitions of these terms, with rates of consensus of more than 80% for each term. The methodology used proved to be a compelling strategy to overcome the current difficulties related to data growth rates and technological convergence in this field. CONCLUSIONS: Our multidisciplinary collaborative approach resulted in consensus definitions that may improve communication, knowledge transfer, collaboration, and research in the rapidly changing field of image-guided minimally invasive techniques.

Multiparametric Magnetic Resonance Imaging for the Detection of Clinically Significant Prostate Cancer: What Urologists Need to Know. Part 3: Targeted Biopsy.

BACKGROUND: After a lesion has been assessed adequately on multiparametric magnetic resonance imaging (mpMRI), magnetic resonance (MR)-guided biopsy (MRGB) is the logical next step. The choice of the MRGB technique, however, is difficult. OBJECTIVE: To show the advantages and disadvantages of the three commonly used MRGB techniques-MRI-ultrasound fusion MRGB (fus-MRGB), direct in-bore MRGB (inbore-MRGB), and cognitive MRGB (cog-MRGB), and to determine when each of the techniques can be used. DESIGN, SETTING, AND PARTICIPANTS: Based on expert opinion and literature overview, the advantages, disadvantages, and challenges of fus-MRGB, inbore-MRGB, and cog-MRGB are evaluated. Further, the clinical setting of each biopsy strategy is assessed. SURGICAL PROCEDURE: Based on expert opinion and literature data, the three biopsy procedures are evaluated, and the important pros and cons are determined. MEASUREMENTS: The basic concept of each biopsy technique is reviewed, which would result in a clinical recommendation. This will be shown in individual patients. RESULTS AND LIMITATIONS: The accompanying video shows how fus-MRGB and inbore-MRGB are performed in our hospital. An important advantage of fus-MRGB is its generally availability; however, it has fusion-error limitations. Although not supported by evidence, inbore-MRGB seems to be better suited for smaller lesions, but is rather expensive. Cog-MRGB is easy to use and inexpensive, but is more operator dependent as it requires knowledge about both ultrasound and MR images. Readers should be aware that our MRGB approach is largely based on expert opinion and, where possible, supported by evidence. CONCLUSIONS: This article and the accompanying video show different MRGB techniques. The advantages and disadvantages of the three biopsy techniques, as well as the clinical setting in which each biopsy strategy is being used in our hospital, are discussed. Fus-MRGB is our first choice for prostate biopsy. Direct inbore-MRGB is used in difficult lesions but is mainly used as a "problem solver" (eg, a negative biopsy with a high suspicion for clinically significant prostate cancer). In our opinion, cog-MRGB is best for sampling larger and diffuse lesions. PATIENT SUMMARY: This third surgery in motion contribution shows our approach in magnetic resonance (MR)-guided biopsy (MRGB). Fusion MRGB is our first choice for prostate biopsy. In-bore MRGB is used in selected, difficult cases, mainly as a problem solver. In our point of view, cognitive MRGB seems to be best for sampling larger lesions and diffuse processes.