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Purpose To evaluate the safety and feasibility of a novel hybrid nuclear and fluoroscopy C-arm scanner to be used during the work-up procedure of hepatic radioembolization. Materials and Methods In this prospective first-in-human clinical study, 12 participants (median age, 67 years [range: 37-78 years]; nine [75%] male, three [25%] female) with liver tumors undergoing work-up for yttrium 90 radioembolization were included (ClinicalTrials.gov NCT06013774). Work-up angiography and technetium 99m-macroaggregated albumin injection were performed in an angiography suite equipped with a hybrid C-arm that could simultaneously perform fluoroscopy and planar nuclear imaging. Technetium 99m-macroaggregated albumin was injected under real-time hybrid imaging, followed by in-room SPECT imaging. Safety and feasibility were studied by assessing adverse events, technical performance, additional x-ray radiation dose, and questionnaires completed by radiologists and technologists. Results No adverse events were attributed to the hybrid C-arm scanner. The additional x-ray radiation dose was low (median, 19 Gy · cm 2 ; minimum: 12 Gy · cm 2 ; maximum: 21 Gy · cm 2 for participants who completed all imaging steps). The interventional personnel considered use of the hybrid C-arm scanner safe and feasible, although the additional time spent in the intervention room was considered long (median, 64 minutes; minimum: 55 minutes; maximum: 77 minutes for participants who completed all imaging steps). Conclusion Use of the hybrid C-arm scanner during the work-up procedure of hepatic radioembolization was found to be safe and feasible in this first-in-human clinical study. Keywords: Angiography, Fluoroscopy, Interventional-Vascular, Radionuclide Studies, Radiosurgery, Gamma Knife, Cyberknife, SPECT, Instrumentation, Physics, Technical Aspects, Technology Assessment Supplemental material is available for this article. Published under a CC BY 4.0 license. Clinical trial registration no. NCT06013774.

Background: Subtraction of single-photon emission computed tomography (SPECT) images has a number of clinical applications in e.g. foci localization in ictal/inter-ictal SPECT and defect detection in rest/stress cardiac SPECT. In this work, we investigated the technical performance of SPECT subtraction for the purpose of quantifying the effect of a vasoconstricting drug (angiotensin-II, or AT2) on the Tc-99m-MAA liver distribution in hepatic radioembolization using an innovative interventional hybrid C-arm scanner. Given that subtraction of SPECT images is challenging due to high noise levels and poor resolution, we compared four methods to obtain a difference image in terms of image quality and quantitative accuracy. These methods included (i) image subtraction: subtraction of independently reconstructed SPECT images, (ii) projection subtraction: reconstruction of a SPECT image from subtracted projections, (iii) projection addition: reconstruction by addition of projections as a background term during the iterative reconstruction, and (iv) image addition: simultaneous reconstruction of the difference image and the subtracted image., Results: Digital simulations (XCAT) and phantom studies (NEMA-IQ and anthropomorphic torso) showed that all four methods were able to generate difference images but their performance on specific metrics varied substantially. Image subtraction had the best quantitative performance (activity recovery coefficient) but had the worst visual quality (contrast-to-noise ratio) due to high noise levels. Projection subtraction showed a slightly better visual quality than image subtraction, but also a slightly worse quantitative accuracy. Projection addition had a substantial bias in its quantitative accuracy which increased with less counts in the projections. Image addition resulted in the best visual image quality but had a quantitative bias when the two images to subtract contained opposing features., Conclusion: All four investigated methods of SPECT subtraction demonstrated the capacity to generate a feasible difference image from two SPECT images. Image subtraction is recommended when the user is only interested in quantitative values, whereas image addition is recommended when the user requires the best visual image quality. Since quantitative accuracy is most important for the dosimetric investigation of AT2 in radioembolization, we recommend using the image subtraction method for this purpose., (© 2024. The Author(s).)

Purpose: Liver metastases presenting as small hyperintense foci on diffusion-weighted imaging (DWI) pose a therapeutic challenge. Ablation is generally not possible since these lesions are often occult on ultrasound and CT. The purpose of this prospective study was to assess if small liver metastases (≤10 mm) detected on DWI can be successfully localized and ablated with the Hepatic Arteriography and C-Arm CT-Guided Ablation technique (HepACAGA)., Materials and Methods: All consecutive patients with small liver metastases (≤10 mm), as measured on DWI, referred for ablation with HepACAGA between 1 January 2021, and 31 October 2023, were included. Re-ablations and ablations concomitant with another local treatment were excluded. The primary outcome was the technical success rate, defined as the intraprocedural detection and subsequent successful ablation of small liver metastases using HepACAGA. Secondary outcomes included the primary and secondary local tumor progression (LTP) rates and the complication rate., Results: A total of 15 patients (26 tumors) were included, with liver metastases from colorectal cancer (73%), neuro-endocrine tumors (15%), breast cancer (8%) and esophageal cancer (4%). All 26 tumors were successfully identified, punctured and ablated (a technical success rate of 100%). After a median follow-up of 9 months, primary and secondary LTP were 4% and 0%, respectively. No complications occurred., Conclusion: In this proof-of-concept study, the HepACAGA technique was successfully used to detect and ablate 100% of small liver metastases identified on DWI with a low recurrence rate and no complications. This technique enables the ablation of subcentimeter liver metastases detected on MRI.

Purpose: Aim of this study was to investigate a dose-response relationship, dose-toxicity relationship, progression free survival (PFS) and overall survival (OS) in neuroendocrine tumour liver metastases (NELM) treated with holmium-166-microspheres radioembolization ([ 166 Ho]-radioembolization)., Materials and Methods: Single center, retrospective study included patients with NELM that received [ 166 Ho]-radioembolization with post-treatment SPECT/CT and CECT or MRI imaging for 3 months follow-up. Post-treatment SPECT/CT was used to calculate tumour (D t ) and whole liver healthy tissue (D h ) absorbed dose. Clinical and laboratory toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE), version 5 at baseline and three-months follow-up. Response was determined according to RECIST 1.1. The tumour and healthy doses was correlated to lesion-based objective response and patient-based toxicity. Kaplan Meier analyses were performed for progression free survival (PFS) and overall survival (OS)., Results: Twenty-seven treatments in 25 patients were included, with a total of 114 tumours. Median follow-up was 14 months (3 - 82 months). Mean D t in non-responders was 68 Gy versus 118 Gy in responders, p = 0.01. ROC analysis determined 86 Gy to have the highest sensitivity and specificity, resp. 83% and 81%. Achieving a D t of ≥ 120 Gy provided the highest likelihood of response (90%) for obtaining response. Sixteen patients had grade 1-2 clinical toxicity and only one patient grade 3. No clear healthy liver dose-toxicity relationship was found. The median PFS was 15 months (95% CI [10.2;19.8]) and median OS was not reached., Conclusion: This study confirms the safety and efficacy of [ 166 Ho]-radioembolization in NELM in a real-world setting. A clear dose-response relationship was demonstrated and future studies should aim at a D t of ≥ 120 Gy, being predictive of response. No dose-toxicity relationship could be established., (© 2024. The Author(s).)

Purpose: Hepatic Arteriography and C-Arm CT-Guided Ablation of liver tumors (HepACAGA) is a novel technique, combining hepatic-arterial contrast injection with C-arm CT-guided navigation. This study compared the outcomes of the HepACAGA technique with patients treated with conventional ultrasound (US) and/or CT-guided ablation., Materials and Methods: In this retrospective cohort study, all consecutive patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLM) treated with conventional US-/CT-guided ablation between 1 January 2015, and 31 December 2020, and patients treated with HepACAGA between 1 January 2021, and 31 October 2023, were included. The primary outcome was local tumor recurrence-free survival (LTRFS). Secondary outcomes included the local tumor recurrence (LTR) rate and complication rate., Results: 68 patients (120 tumors) were included in the HepACAGA cohort and 53 patients (78 tumors) were included in the conventional cohort. In both cohorts, HCC was the predominant tumor type (63% and 73%, respectively). In the HepACAGA cohort, all patients received microwave ablation. Radiofrequency ablation was the main ablation technique in the conventional group (78%). LTRFS was significantly longer for patients treated with the HepACAGA technique ( p = 0.015). Both LTR and the complication rate were significantly lower in the HepACAGA cohort compared to the conventional cohort (LTR 5% vs. 26%, respectively; p < 0.001) (complication rate 4% vs. 15%, respectively; p = 0.041)., Conclusions: In this study, the HepACAGA technique was safer and more effective than conventional ablation for HCC and CRLM, resulting in lower rates of local tumor recurrence, longer local tumor recurrence-free survival and fewer procedure-related complications.

Background: Although CT perfusion (CTP) is often incorporated in acute stroke workflows, it remains largely unclear what the associated costs and health implications are in the long run of CTP-based patient selection for endovascular treatment (EVT) in patients presenting within 6 hours after symptom onset with a large vessel occlusion., Methods: Patients with a large vessel occlusion were included from a Dutch nationwide cohort (n=703) if CTP imaging was performed before EVT within 6 hours after stroke onset. Simulated cost and health effects during 5 and 10 years follow-up were compared between CTP based patient selection for EVT and providing EVT to all patients. Outcome measures were the net monetary benefit at a willingness-to-pay of €80 000 per quality-adjusted life year, incremental cost-effectiveness ratio), difference in costs from a healthcare payer perspective (ΔCosts) and quality-adjusted life years (ΔQALY) per 1000 patients for 1000 model iterations as outcomes., Results: Compared with treating all patients, CTP-based selection for EVT at the optimised ischaemic core volume (ICV≥110 mL) or core-penumbra mismatch ratio (MMR≤1.4) thresholds resulted in losses of health (median ΔQALYs for ICV≥110 mL: -3.3 (IQR: -5.9 to -1.1), for MMR≤1.4: 0.0 (IQR: -1.3 to 0.0)) with median ΔCosts for ICV≥110 mL of -€348 966 (IQR: -€712 406 to -€51 158) and for MMR≤1.4 of €266 513 (IQR: €229 403 to €380 110)) per 1000 patients. Sensitivity analyses did not yield any scenarios for CTP-based selection of patients for EVT that were cost-effective for improving health, including patients aged ≥80 years CONCLUSION: In EVT-eligible patients presenting within 6 hours after symptom onset, excluding patients based on CTP parameters was not cost-effective and could potentially harm patients., Competing Interests: Competing interests: BJE reports grants from LtC (ZonMW and TKI-PPP of Health Holland). WHvZ reports speaker fees from Cerenovus, NicoLab and Stryker, and consulting fees from Philips, all paid to Institution. DWJD report grants from the Dutch Heart Foundation, Brain Foundation Netherlands, ZON MW, Stryker, Medtronic, Cerenovus, Thrombolytic Science, received by the Erasmus University Medical Center outside this project. AJY reports Research grants from Medtronic, Cerenovus, Penumbra, Stryker, and Genentech. Consultant for Penumbra, Cerenovus, Nicolab, Philips, Vesalio, Zoll Circulation, and NIH/NINDS. CBM: grants from Healthcare Evaluation Netherlands, CVON/Dutch Heart Foundation, TWIN foundation and Stryker during the conduct of the study and from European Commission outside this project (all paid to institution) and is shareholder of Nicolab. All other contributors report no other conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Recent studies have shown a clear relationship between absorbed dose and tumor response to treatment after hepatic radioembolization. These findings help to create more personalized treatment planning and dosimetry. However, crucial to this goal is the ability to predict the dose distribution prior to treatment. The microsphere distribution is ultimately determined by (i) the hepatic vasculature and the resulting blood flow dynamics and (ii) the catheter position., Purpose: To show that pretreatment, intra-procedural imaging of blood flow patterns, as quantified by catheter-directed intra-arterial contrast enhancement, correlate with posttreatment microsphere accumulation and, consequently, absorbed dose., Materials and Methods: Patients who participated in a clinical trial (NCT01177007) and for whom both a pretreatment dual-phase contrast-enhanced cone-beam CT (CBCT) and a posttreatment 90Y PET/CT scan were available were included in this retrospective study. Tumors and perfused volumes were manually delineated on the CBCT by an experienced radiologist. The mean, sum, and standard deviation of the voxels in each volume were recorded. The delineations were transferred to the PET-based absorbed dose maps by coregistration of the corresponding CTs. Linear multiple regression was used to correlate pretreatment CBCT enhancement to posttreatment 90Y PET/CT-based absorbed dose in each region. Leave-one-out cross-validation and Bland-Altman analyses were performed on the predicted versus measured absorbed doses., Results: Nine patients, with a total of 23 tumors were included. All presented with hepatocellular carcinoma (HCC). Visually, all patients had a clear correspondence between CBCT enhancement and absorbed dose. The correlation between CBCT enhancement and posttherapy absorbed tumor dose based was strong (R 2  = 0.91), and moderate for the non-tumor liver tissue (R 2  = 0.61). Limits of agreement were approximately ±55 Gray for tumor tissue., Conclusion: There is a linear relationship between pretreatment blood dynamics in HCC tumors and posttreatment absorbed dose, which, if shown to be generalizable, allows for pretreatment tumor absorbed dose prediction., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objectives: CT perfusion (CTP) has been suggested to increase the rate of large vessel occlusion (LVO) detection in patients suspected of acute ischemic stroke (AIS) if used in addition to a standard diagnostic imaging regime of CT angiography (CTA) and non-contrast CT (NCCT). The aim of this study was to estimate the costs and health effects of additional CTP for endovascular treatment (EVT)-eligible occlusion detection using model-based analyses., Methods: In this Dutch, nationwide retrospective cohort study with model-based health economic evaluation, data from 701 EVT-treated patients with available CTP results were included (January 2018-March 2022; trialregister.nl:NL7974). We compared a cohort undergoing NCCT, CTA, and CTP (NCCT + CTA + CTP) with a generated counterfactual where NCCT and CTA (NCCT + CTA) was used for LVO detection. The NCCT + CTA strategy was simulated using diagnostic accuracy values and EVT effects from the literature. A Markov model was used to simulate 10-year follow-up. We adopted a healthcare payer perspective for costs in euros and health gains in quality-adjusted life years (QALYs). The primary outcome was the net monetary benefit (NMB) at a willingness to pay of €80,000; secondary outcomes were the difference between LVO detection strategies in QALYs (ΔQALY) and costs (ΔCosts) per LVO patient., Results: We included 701 patients (median age: 72, IQR: [62-81]) years). Per LVO patient, CTP-based occlusion detection resulted in cost savings (ΔCosts median: € - 2671, IQR: [€ - 4721; € - 731]), a health gain (ΔQALY median: 0.073, IQR: [0.044; 0.104]), and a positive NMB (median: €8436, IQR: [5565; 11,876]) per LVO patient., Conclusion: CTP-based screening of suspected stroke patients for an endovascular treatment eligible large vessel occlusion was cost-effective., Clinical Relevance Statement: Although CTP-based patient selection for endovascular treatment has been recently suggested to result in worse patient outcomes after ischemic stroke, an alternative CTP-based screening for endovascular treatable occlusions is cost-effective., Key Points: • Using CT perfusion to detect an endovascular treatment-eligible occlusions resulted in a health gain and cost savings during 10 years of follow-up. • Depending on the screening costs related to the number of patients needed to image with CT perfusion, cost savings could be considerable (median: € - 3857, IQR: [€ - 5907; € - 1916] per patient). • As the gain in quality adjusted life years was most affected by the sensitivity of CT perfusion-based occlusion detection, additional studies for the diagnostic accuracy of CT perfusion for occlusion detection are required., (© 2023. The Author(s).)

Purpose: Radiation pneumonitis is a serious complication of radioembolization. In holmium-166 ([ 166 Ho]) radioembolization, the lung mean dose (LMD) can be estimated (eLMD) using a scout dose with either technetium-99 m-macroaggregated albumin ([ 99m Tc]MAA) or [ 166 Ho]-microspheres. The accuracy of eLMD based on [ 99m Tc]MAA (eLMD MAA ) was compared to eLMD based on [ 166 Ho]-scout dose (eLMD Ho-scout ) in two prospective clinical studies., Materials and Methods: Patients were included if they received both scout doses ([ 99m Tc]MAA and [ 166 Ho]-scout), had a posttreatment [ 166 Ho]-SPECT/CT (gold standard) and were scanned on the same hybrid SPECT/CT system. The correlation between eLMD MAA /eLMD Ho-scout and LMD Ho-treatment was assessed by Spearman's rank correlation coefficient (r). Wilcoxon signed rank test was used to analyze paired data., Results: Thirty-seven patients with unresectable liver metastases were included. During follow-up, none developed symptoms of radiation pneumonitis. Median eLMD MAA (1.53 Gy, range 0.09-21.33 Gy) was significantly higher than median LMD Ho-treatment (0.00 Gy, range 0.00-1.20 Gy; p < 0.01). Median eLMD Ho-scout (median 0.00 Gy, range 0.00-1.21 Gy) was not significantly different compared to LMD Ho-treatment (p > 0.05). In all cases, eLMD MAA was higher than LMD Ho-treatment (p < 0.01). While a significant correlation was found between eLMD Ho-scout and LMD Ho-treatment (r = 0.43, p < 0.01), there was no correlation between eLMD MAA and LMD Ho-treatment (r = 0.02, p = 0.90)., Conclusion: [ 166 Ho]-scout dose is superior in predicting LMD over [ 99m Tc]MAA, in [ 166 Ho]-radioembolization. Consequently, [ 166 Ho]-scout may limit unnecessary patient exclusions and avoid unnecessary therapeutic activity reductions in patients eligible for radioembolization., Trail Registration: NCT01031784, registered December 2009. NCT01612325, registered June 2012., (© 2024. The Author(s).)

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90 Y-glass, 90 Y-resin, and 166 Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90 Y PET/CT and quantitative 166 Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [ 18 F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90 Y-glass, 8 90 Y-resin, and 7 166 Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90 Y-glass, 1.5 GBq for 90 Y-resin, and 7.0 GBq for 166 Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90 Y-glass than for 90 Y-resin and 166 Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90 Y-glass vs. 73 Gy for 90 Y-resin and 50 Gy for 166 Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90 Y-glass vs. 37 Gy for 90 Y-resin and 31 Gy for 166 Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [ 18 F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: We aimed to evaluate the real-world variation in CT perfusion (CTP) imaging protocols among stroke centers and to explore the potential for standardizing vendor software to harmonize CTP images., Methods: Stroke centers participating in a nationwide multicenter healthcare evaluation were requested to share their CTP scan and processing protocol. The impact of these protocols on CTP imaging was assessed by analyzing data from an anthropomorphic phantom with center-specific vendor software with default settings from one of three vendors (A-C): IntelliSpace Portal, syngoVIA, and Vitrea. Additionally, standardized infarct maps were obtained using a logistic model., Results: Eighteen scan protocols were studied, all varying in acquisition settings. Of these protocols, seven, eight, and three were analyzed with center-specific vendor software A, B, and C respectively. The perfusion maps were visually dissimilar between the vendor software but were relatively unaffected by the acquisition settings. The median error [interquartile range] of the infarct core volumes (mL) estimated by the vendor software was - 2.5 [6.5] (A)/ - 18.2 [1.2] (B)/ - 8.0 [1.4] (C) when compared to the ground truth of the phantom (where a positive error indicates overestimation). Taken together, the median error [interquartile range] of the infarct core volumes (mL) was - 8.2 [14.6] before standardization and - 3.1 [2.5] after standardization., Conclusions: CTP imaging protocols varied substantially across different stroke centers, with the perfusion software being the primary source of differences in CTP images. Standardizing the estimation of ischemic regions harmonized these CTP images to a degree., Clinical Relevance Statement: The center that a stroke patient is admitted to can influence the patient's diagnosis extensively. Standardizing vendor software for CT perfusion imaging can improve the consistency and accuracy of results, enabling a more reliable diagnosis and treatment decision., Key Points: • CT perfusion imaging is widely used for stroke evaluation, but variation in the acquisition and processing protocols between centers could cause varying patient diagnoses. • Variation in CT perfusion imaging mainly arises from differences in vendor software rather than acquisition settings, but these differences can be reconciled by standardizing the estimation of ischemic regions. • Standardizing the estimation of ischemic regions can improve CT perfusion imaging for stroke evaluation by facilitating reliable evaluations independent of the admission center., (© 2023. The Author(s).)

Background: With the introduction of prostate specific membrane antigen (PSMA) PET/CT, the detection rate of prostate cancer metastases has improved significantly, both for primary staging and for biochemical recurrence. EANM/SNMMI guidelines recommend a 60 min time interval between [ 68 Ga]Ga-PSMA administration and acquisition., Purpose: This study evaluates the possibility of a shorter time interval by investigating the dynamic change in image quality measures., Method: We retrospectively analyzed 10 consecutive prostate cancer patients who underwent a dynamic whole body [ 68 Ga]Ga-PSMA-11 PET/CT of 75 min from skull vertex to mid-thigh using Siemens FlowMotion. PET images were acquired directly after injection of 1.5 MBq/kg [ 68 Ga]Ga-PSMA-11. Image quality measures included lesion maximum standardized uptake value corrected for lean body mass (SUL max ), tumor-to-background ratio (TBR), and contrast-to-noise ratio (CNR). Quantitative analysis of image quality in dynamic PET was performed using PMOD (version 4.2). Regions of interest (ROIs), drawn included different types of prostate lesions (primary tumor, lymph nodes, and bone metastasis), organ tissue (liver, spleen, lacrimal gland, submandibular gland, parotid gland, urinary bladder, kidneys blood pool [ascending aorta], left ventricle), bone tissue (4th lumbar vertebral body [L4]) and muscle tissue (gluteus maximus). To further investigate image quality four 10 min multi-frame reconstructions with clinical parameters were made at different post-injection times (15, 30, 45, and 60 min). A nuclear medicine physician performed a blinded lesion detectability evaluation on these multi-frame reconstructions for different prostate cancer lesions., Results: Six primary prostate tumors in seven patients with prostate in situ, 13 lymph node metastases in six patients and up to 12 bone metastases in three patients were found. The different prostate lesion types (lymph nodes metastases, bone metastases, and primary prostate tumor) all show an increase in average SUL max , TBR, and CNR over time during the scan. The normalized average SUL max , TBR, and CNR of the combined prostate lesions at 15, 30, and 45 min post-injection scans were all significant p < 0.05 lower from the 60 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT (9.5 ± 4.5, 12.7 ± 6.2, and 41.8 ± 24.5, respectively). At patient level, the reader concluded the same regarding the presence/absence of primary prostate cancer recurrence, lymph node metastases, and/or bone metastases on all <60 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT's in comparison to the reference scan (60 min post-injection). At lesion level, all bone metastases seen on the reference scan were also seen on all <60 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT's but there were some lymph nodes (n = 2) metastases missed on the 15, 30, and 45 min post-injection scans. One lymph node metastasis on both the 15 and 30 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT's was missed and one lymph node metastasis was missed, only on the 45 min post-injection [ 68 Ga]Ga-PSMA-11 PET/CT., Conclusion: Shorter post-injection times (15, 30, and 45 min) compared to the recommended post-injection time of 60 min are not optimal. However, the impact of a shorter time interval of 45 min instead of 60 min between [ 68 Ga]Ga-PSMA-11 administration and the start of PET/CT acquisition on both image quality (SUL max , TBR, and CNR) and lesion detection, while significant, is small., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: For safe and effective holmium-166 ( 166 Ho) liver radioembolization, dosimetry is crucial and requires accurate healthy liver definition. The current clinical standard relies on manual segmentation and registration of a separately acquired contrast enhanced CT (CECT), a prone-to-error and time-consuming task. An alternative is offered by simultaneous imaging of 166 Ho and technetium-99m stannous-phytate accumulating in healthy liver cells ( 166 Ho- 99m Tc dual-isotope protocol). This study compares healthy liver segmentation performed with an automatic method using 99m Tc images derived from a 166 Ho- 99m Tc dual-isotope acquisition to the manual segmentation, focusing on healthy liver dosimetry and corresponding hepatotoxicity. Data from the prospective HEPAR PLuS study were used. Automatic healthy liver segmentation was obtained by thresholding the 99m Tc image (no registration step required). Manual segmentation was performed on CECT and then manually registered to the SPECT/CT and subsequently to the corresponding 166 Ho SPECT to compute absorbed dose in healthy liver., Results: Thirty-one patients (66 procedures) were assessed. Manual segmentation and registration took a median of 30 min per patient, while automatic segmentation was instantaneous. Mean ± standard deviation of healthy liver absorbed dose was 18 ± 7 Gy and 20 ± 8 Gy for manual and automatic segmentations, respectively. Mean difference ± coefficient of reproducibility between healthy liver absorbed doses using the automatic versus manual segmentation was 2 ± 6 Gy. No correlation was found between mean absorbed dose in the healthy liver and hepatotoxicity., Conclusions: 166 Ho- 99m Tc dual-isotope protocol can automatically segment the healthy liver without hampering the 166 Ho dosimetry assessment., Trial Registration: ClinicalTrials.gov, NCT02067988. Registered 20 February 2014. https://clinicaltrials.gov/ct2/show/NCT02067988., (© 2023. The Author(s).)

Introduction: Locating a vessel occlusion is important for clinical decision support in stroke healthcare. The advent of endovascular thrombectomy beyond proximal large vessel occlusions spurs alternative approaches to locate vessel occlusions. We explore whether CT perfusion (CTP) data can help to automatically locate vessel occlusions., Methods: We composed an atlas with the downstream regions of particular vessel segments. Occlusion of these segments should result in the hypoperfusion of the corresponding downstream region. We differentiated between seven-vessel occlusion locations (ICA, proximal M1, distal M1, M2, M3, ACA, and posterior circulation). We included 596 patients from the DUtch acute STroke (DUST) multicenter study. Each patient CTP data set was processed with perfusion software to determine the hypoperfused region. The downstream region with the highest overlap with the hypoperfused region was considered to indicate the vessel occlusion location. We assessed the indications from CTP against expert annotations from CTA., Results: Our atlas-based model had a mean accuracy of 86% and could achieve substantial agreement with the annotations from CTA according to Cohen's kappa coefficient (up to 0.68). In particular, anterior large vessel occlusions and occlusions in the posterior circulation could be located with an accuracy of 80 and 92%, respectively., Conclusion: The spatial layout of the hypoperfused region can help to automatically indicate the vessel occlusion location for acute ischemic stroke patients. However, variations in vessel architecture between patients seemed to limit the capacity of CTP data to distinguish between vessel occlusion locations more accurately., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peerlings, de Jong, Bennink, Dankbaar, Velthuis, Emmer, Majoie and Marquering.)

Background: Identifying cardioembolic sources in patients with acute ischemic stroke is important for the choice of secondary prevention strategies. We prospectively investigated the yield of admission (spectral) nongated cardiac computed tomography angiography (CTA) to detect cardioembolic sources in stroke., Methods: Participants of the ENCLOSE study (Improved Prediction of Recurrent Stroke and Detection of Small Volume Stroke) with transient ischemic attack or acute ischemic stroke with assessable nongated head-to-heart CTA at the University Medical Center Utrecht were included between June 2017 and March 2022. The presence of cardiac thrombus on cardiac CTA was based on a Likert scale and dichotomized into certainly or probably absent versus possibly, probably, or certainly present. The diagnostic certainty of cardiac thrombus was evaluated again on spectral computed tomography reconstructions. The likelihood of a cardioembolic source was determined post hoc by an expert panel in patients with cardiac thrombus on CTA. Parametric and nonparametric tests were used to compare the outcome groups., Results: Forty four (12%) of 370 included patients had a cardiac thrombus on admission CTA: 35 (9%) in the left atrial appendage and 14 (4%) in the left ventricle. Patients with cardiac thrombus had more severe strokes (median National Institutes of Health Stroke Scale score, 10 versus 4; P =0.006), had higher clot burden (median clot burden score, 9 versus 10; P =0.004), and underwent endovascular treatment more often (43% versus 20%; P <0.001) than patients without cardiac thrombus. Left atrial appendage thrombus was present in 28% and 6% of the patients with and without atrial fibrillation, respectively ( P <0.001). The diagnostic certainty for left atrial appendage thrombus was higher for spectral iodine maps compared with the conventional CTA ( P <0.001). The presence of cardiac thrombus on CTA increased the likelihood of a cardioembolic source according to the expert panel ( P <0.001)., Conclusions: Extending the stroke CTA to cover the heart increases the chance of detecting cardiac thrombi and helps to identify cardioembolic sources in the acute stage of ischemic stroke with more certainty. Spectral iodine maps provide additional value for detecting left atrial appendage thrombus., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04019483.

Since its first suggestion as possible option for liver radioembolization treatment, the therapeutic isotope holmium-166 ( 166 Ho) caught the experts' attention due to its imaging possibilities. Being not only a beta, but also a gamma emitter and a lanthanide, 166 Ho can be imaged using single-photon emission computed tomography and magnetic resonance imaging, respectively. Another advantage of 166 Ho is the possibility to perform the scout and treatment procedure with the same particle. This prospect paves the way to an individualized treatment procedure, gaining more control over dosimetry-based patient selection and treatment planning. In this review, an overview on 166 Ho liver radioembolization will be presented. The current clinical workflow, together with the most relevant clinical findings and the future prospective will be provided., (© 2022. The Author(s).)

Objectives: To compare single parameter thresholding with multivariable probabilistic classification of ischemic stroke regions in the analysis of computed tomography perfusion (CTP) parameter maps., Methods: Patients were included from two multicenter trials and were divided into two groups based on their modified arterial occlusive lesion grade. CTP parameter maps were generated with three methods-a commercial method (ISP), block-circulant singular value decomposition (bSVD), and non-linear regression (NLR). Follow-up non-contrast CT defined the follow-up infarct region. Conventional thresholds for individual parameter maps were established with a receiver operating characteristic curve analysis. Probabilistic classification was carried out with a logistic regression model combining the available CTP parameters into a single probability., Results: A total of 225 CTP data sets were included, divided into a group of 166 patients with successful recanalization and 59 with persistent occlusion. The precision and recall of the CTP parameters were lower individually than when combined into a probability. The median difference [interquartile range] in mL between the estimated and follow-up infarct volume was 29/23/23 [52/50/52] (ISP/bSVD/NLR) for conventional thresholding and was 4/6/11 [31/25/30] (ISP/bSVD/NLR) for the probabilistic classification., Conclusions: Multivariable probability maps outperform thresholded CTP parameter maps in estimating the infarct lesion as observed on follow-up non-contrast CT. A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions., Key Points: • Combining CTP parameters with a logistic regression model increases the precision and recall in estimating ischemic stroke regions. • Volumes following from a probabilistic analysis predict follow-up infarct volumes better than volumes following from a threshold-based analysis. • A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions., (© 2022. The Author(s).)

Background and Purpose: Dual-energy virtual NCCT has the potential to replace conventional NCCT to detect early ischemic changes in acute ischemic stroke. In this study, we evaluated whether virtual NCCT is noninferior compared with standard linearly blended NCCT, a surrogate of conventional NCCT, regarding the detection of early ischemic changes with ASPECTS., Materials and Methods: Adult patients who presented with suspected acute ischemic stroke and who underwent dual-energy NCCT and CTA and brain MR imaging within 48 hours were included. Standard linearly blended images were reconstructed to match a conventional NCCT. Virtual NCCT images were reconstructed from CTA. ASPECTS was evaluated on conventional NCCT, virtual NCCT, and DWI, which served as the reference standard. Agreement between CT assessments and the reference standard was evaluated with the Lin concordance correlation coefficient. Noninferiority was assessed with bootstrapped estimates of the differences in ASPECTS between conventional and virtual NCCT with 95% CIs., Results: Of the 193 included patients, 100 patients (52%) had ischemia on DWI. Compared with the reference standard, the ASPECTS concordance correlation coefficient for conventional and virtual NCCT was 0.23 (95% CI, 0.15-0.32) and 0.44 (95% CI, 0.33-0.53), respectively. The difference in the concordance correlation coefficient between virtual and conventional NCCT was 0.20 (95% CI, 0.01-0.39) and did not cross the prespecified noninferiority margin of -0.10., Conclusions: Dual-energy virtual NCCT is noninferior compared with conventional NCCT for the detection of early ischemic changes with ASPECTS., (© 2022 by American Journal of Neuroradiology.)

Radiation pneumonitis is a rare but possibly fatal side effect of 90 Y radioembolization. It may occur 1-6 mo after therapy, if a significant part of the 90 Y microspheres shunts to the lungs. In current clinical practice, a predicted lung dose greater than 30 Gy is considered a criterion to exclude patients from treatment. However, contrasting findings regarding the occurrence of radiation pneumonitis and lung dose were previously reported in the literature. In this study, the relationship between the lung dose and the eventual occurrence of radiation pneumonitis after 90 Y radioembolization was investigated. Methods: We retrospectively analyzed 317 90 Y liver radioembolization procedures performed during an 8-y period (February 2012 to September 2020). We calculated the predicted lung mean dose (LMD) using 99m Tc-MAA planar scintigraphy (LMD MAA ) acquired during the planning phase and left LMD (LMD Y-90 ) using the 90 Y PET/CT acquired after the treatment. For the lung dose computation, we used the left lung as the representative lung volume, to compensate for scatter from the liver moving in the craniocaudal direction because of breathing and mainly affecting the right lung. Results: In total, 272 patients underwent 90 Y procedures, of which 63% were performed with glass microspheres and 37% with resin microspheres. The median injected activity was 1,974 MBq (range, 242-9,538 MBq). The median LMD MAA was 3.5 Gy (range, 0.2-89.0 Gy). For 14 procedures, LMD MAA was more than 30 Gy. Median LMD Y-90 was 1 Gy (range, 0.0-22.1 Gy). No patients had an LMD Y-90 of more than 30 Gy. Of the 3 patients with an LMD Y-90 of more than 12 Gy, 2 patients (one with an LMD Y-90 of 22.1 Gy and an LMD MAA of 89 Gy; the other with an LMD Y-90 of 17.7 Gy and an LMD MAA of 34.1 Gy) developed radiation pneumonitis and consequently died. The third patient, with an LMD Y-90 of 18.4 Gy (LMD MAA , 29.1 Gy), died 2 mo after treatment, before the imaging evaluation, because of progressive disease. Conclusion: The occurrence of radiation pneumonitis as a consequence of a lung shunt after 90 Y radioembolization is rare (<1%). No radiation pneumonitis developed in patients with a measured LMD Y-90 lower than 12 Gy., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Introduction: Handheld gamma cameras and gamma probes have been successfully implemented for enabling nuclear image or radio-guidance in minimally-invasive procedures. There is an opportunity for large field-of-view interventional planar scintigraphy and SPECT imaging to complement these small field-of-view devices for two reasons. First, a large field-of-view camera enables imaging of relatively larger organs and activity accumulations that are not close to the patient's skin. And second, more precise corrections can be implemented in the SPECT reconstruction algorithm, improving its quality., Areas Covered: This review article discusses the progress that has been made in the field of large field-of-view interventional planar scintigraphy and SPECT imaging. First, an overview of planar scintigraphy and SPECT is provided. Second, an exploration is given of the potential applications where large field-of-view interventional planar scintigraphy and SPECT imaging may be employed. And third, the requirements for scanner hardware are discussed and an overview of the possible system configurations is provided., Expert Opinion: We believe that there is an opportunity for large field-of-view interventional planar scintigraphy and SPECT imaging to assist clinical workflows. A major effort is now required to evaluate the prototype systems in clinical studies so that valuable practical experience can be obtained.

Background: Partition modeling allows personalized activity calculation for holmium-166 ( 166 Ho) radioembolization. However, it requires the definition of tumor and non-tumorous liver, by segmentation and registration of a separately acquired CT, which is time-consuming and prone to error. A protocol including 166 Ho-scout, for treatment simulation, and technetium-99m ( 99m Tc) stannous phytate for healthy-liver delineation was proposed. This study assessed the accuracy of automatic healthy-liver segmentation using 99m Tc images derived from a phantom experiment. In addition, together with data from a patient study, the effect of different 99m Tc activities on the 166 Ho-scout images was investigated. To reproduce a typical scout procedure, the liver compartment, including two tumors, of an anthropomorphic phantom was filled with 250 MBq of 166 Ho-chloride, with a tumor to non-tumorous liver activity concentration ratio of 10. Eight SPECT/CT scans were acquired, with varying levels of 99m Tc added to the non-tumorous liver compartment (ranging from 25 to 126 MBq). For comparison, forty-two scans were performed in presence of only 99m Tc from 8 to 240 MBq. 99m Tc image quality was assessed by cold-sphere (tumor) contrast recovery coefficients. Automatic healthy-liver segmentation, obtained by thresholding 99m Tc images, was evaluated by recovered volume and Sørensen-Dice index. The impact of 99m Tc on 166 Ho images and the role of the downscatter correction were evaluated on phantom scans and twenty-six patients' scans by considering the reconstructed 166 Ho count density in the healthy-liver., Results: All 99m Tc image reconstructions were found to be independent of the 166 Ho activity present during the acquisition. In addition, cold-sphere contrast recovery coefficients were independent of 99m Tc activity. The segmented healthy-liver volume was recovered fully, independent of 99m Tc activity as well. The reconstructed 166 Ho count density was not influenced by 99m Tc activity, as long as an adequate downscatter correction was applied., Conclusion: The 99m Tc image reconstructions of the phantom scans all performed equally well for the purpose of automatic healthy-liver segmentation, for activities down to 8 MBq. Furthermore, 99m Tc could be injected up to at least 126 MBq without compromising 166 Ho image quality. Clinical trials The clinical study mentioned is registered with Clinicaltrials.gov (NCT02067988) on February 20, 2014., (© 2022. The Author(s).)

Background: A considerable proportion of acute ischemic stroke patients treated with endovascular thrombectomy (EVT) are dead or severely disabled at 3 months despite successful reperfusion. Ischemic core imaging biomarkers may help to identify patients who are more likely to have a poor outcome after endovascular thrombectomy (EVT) despite successful reperfusion. We studied the association of CT perfusion-(CTP), CT angiography-(CTA), and non-contrast CT-(NCCT) based imaging markers with poor outcome in patients who underwent EVT in daily clinical practice. Methods: We included EVT-treated patients (July 2016-November 2017) with an anterior circulation occlusion from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry with available baseline CTP, CTA, and NCCT. We used multivariable binary and ordinal logistic regression to analyze the association of CTP ischemic core volume, CTA-Collateral Score (CTA-CS), and Alberta Stroke Program Early CT Score (ASPECTS) with poor outcome (modified Rankin Scale score (mRS) 5-6) and likelihood of having a lower score on the mRS at 90 days. Results: In 201 patients, median core volume was 13 (IQR 5-41) mL. Median ASPECTS was 9 (IQR 8-10). Most patients had grade 2 (83/201; 42%) or grade 3 (28/201; 14%) collaterals. CTP ischemic core volume was associated with poor outcome [aOR per 10 mL 1.02 (95%CI 1.01-1.04)] and lower likelihood of having a lower score on the mRS at 90 days [aOR per 10 mL 0.85 (95% CI 0.78-0.93)]. In multivariable analysis, neither CTA-CS nor ASPECTS were significantly associated with poor outcome or the likelihood of having a lower mRS. Conclusion: In our population of patients treated with EVT in daily clinical practice, CTP ischemic core volume is associated with poor outcome and lower likelihood of shift toward better outcome in contrast to either CTA-CS or ASPECTS., Competing Interests: BE reports grants from LtC (ZonMW and TKI-PPP of Health Holland outside the submitted work. WZ reports personal fees from Cerenovus and from Stryker outside the submitted work. DD reports grants from the Dutch Heart Foundation, AngioCare, Medtronic/Covidien/EV3, MEDAC/LAMEPRO, Penumbra, Top Medical/Concentric, and Stryker during conduct of the study; consultation fees from Stryker, Bracco Imaging, and Servier, received by the Erasmus University Medical Centre, outside the submitted work. CM reports grants from TWIN, during the conduct of the study and grants from CVON/Dutch Heart Foundation, European Commission, Dutch Health Evaluation Program, and from Stryker outside the submitted work (paid to institution) and is shareholder of NICO.LAB. HM is co-founder and shareholder of NICO.LAB. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Koopman, Hoving, Kappelhof, Berkhemer, Beenen, van Zwam, de Jong, Dankbaar, Dippel, Coutinho, Marquering, Emmer and Majoie.)

Purpose: This study evaluates the performance of a mobile and compact hybrid C-arm scanner (referred to as IXSI) that is capable of simultaneous acquisition of 2D fluoroscopic and nuclear projections and 3D image reconstruction in the intervention room., Results: The impact of slightly misaligning the IXSI modalities (in an off-focus geometry) was investigated for the reduction of the fluoroscopic and nuclear interference. The 2D and 3D nuclear image quality of IXSI was compared with a clinical SPECT/CT scanner by determining the spatial resolution and sensitivity of point sources and by performing a quantitative analysis of the reconstructed NEMA image quality phantom. The 2D and 3D fluoroscopic image of IXSI was compared with a clinical CBCT scanner by visualizing the Fluorad A+D image quality phantom and by visualizing a reconstructed liver nodule phantom. Finally, the feasibility of dynamic simultaneous nuclear and fluoroscopic imaging was demonstrated by injecting an anthropomorphic phantom with a mixture of iodinated contrast and 99m Tc., Conclusion: Due to the divergent innovative hybrid design of IXSI, concessions were made to the nuclear and fluoroscopic image qualities. Nevertheless, IXSI realizes unique image guidance that may be beneficial for several types of procedures., Key Points: • IXSI can perform time-resolved planar (2D) simultaneous fluoroscopic and nuclear imaging. • IXSI can perform SPECT/CBCT imaging (3D) inside the intervention room., (© 2021. The Author(s).)

Objectives: To report the variation in computed tomography perfusion (CTP) arterial input function (AIF) in a multicenter stroke study and to assess the impact this has on CTP results., Methods: CTP datasets from 14 different centers were included from the DUtch acute STroke (DUST) study. The AIF was taken as a direct measure to characterize contrast bolus injection. Statistical analysis was applied to evaluate differences in amplitude, area under the curve (AUC), bolus arrival time (BAT), and time to peak (TTP). To assess the clinical relevance of differences in AIF, CTP acquisitions were simulated with a realistic anthropomorphic digital phantom. Perfusion parameters were extracted by CTP analysis using commercial software (IntelliSpace Portal (ISP), version 10.1) as well as an in-house method based on block-circulant singular value decomposition (bSVD)., Results: A total of 1422 CTP datasets were included, ranging from 6 to 322 included patients per center. The measured values of the parameters used to characterize the AIF differed significantly with approximate interquartile ranges of 200-750 HU for the amplitude, 2500-10,000 HU·s for the AUC, 0-17 s for the BAT, and 10-26 s for the TTP. Mean infarct volumes of the phantom were significantly different between centers for both methods of perfusion analysis., Conclusions: Although guidelines for the acquisition protocol are often provided for centers participating in a multicenter study, contrast medium injection protocols still vary. The resulting volumetric differences in infarct core and penumbra may impact clinical decision making in stroke diagnosis., Key Points: • The contrast medium injection protocol may be different between stroke centers participating in a harmonized multicenter study. • The contrast medium injection protocol influences the results of X-ray computed tomography perfusion imaging. • The contrast medium injection protocol can impact stroke diagnosis and patient selection for treatment., (© 2021. The Author(s).)

Rationale and Objectives: To evaluate the image quality of virtual monochromatic images (VMI) reconstructed from dual-energy dual-source noncontrast head CT with different reconstruction kernels., Materials and Methods: Twenty-five consecutive adult patients underwent noncontrast dual-energy CT. VMI were retrospectively reconstructed at 5-keV increments from 40 to 140 keV using quantitative and head kernels. CT-number, noise levels (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in the gray and white matter and artifacts using the posterior fossa artifact index (PFAI) were evaluated., Results: CT-number increased with decreasing VMI energy levels, and SD was lowest at 85 keV. SNR was maximized at 80 keV and 85 keV for the head and quantitative kernels, respectively. CNR was maximum at 40 keV; PFAI was lowest at 90 (head kernel) and 100 (quantitative kernel) keV. Optimal VMI image quality was significantly better than conventional CT., Conclusion: Optimal image quality of VMI energies can improve brain parenchymal image quality compared to conventional CT but are reconstruction kernel dependent and depend on indication for performing noncontrast CT., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate whether the addition of brain CT imaging data to a model incorporating clinical risk factors improves prediction of ischemic stroke recurrence over 5 years of follow-up., Methods: A total of 638 patients with ischemic stroke from three centers were selected from the Dutch acute stroke study (DUST). CT-derived candidate predictors included findings on non-contrast CT, CT perfusion, and CT angiography. Five-year follow-up data were extracted from medical records. We developed a multivariable Cox regression model containing clinical predictors and an extended model including CT-derived predictors by applying backward elimination. We calculated net reclassification improvement and integrated discrimination improvement indices. Discrimination was evaluated with the optimism-corrected c-statistic and calibration with a calibration plot., Results: During 5 years of follow-up, 56 patients (9%) had a recurrence. The c-statistic of the clinical model, which contained male sex, history of hyperlipidemia, and history of stroke or transient ischemic attack, was 0.61. Compared with the clinical model, the extended model, which contained previous cerebral infarcts on non-contrast CT and Alberta Stroke Program Early CT score greater than 7 on mean transit time maps derived from CT perfusion, had higher discriminative performance (c-statistic 0.65, P = 0.01). Inclusion of these CT variables led to a significant improvement in reclassification measures, by using the net reclassification improvement and integrated discrimination improvement indices., Conclusion: Data from CT imaging significantly improved the discriminatory performance and reclassification in predicting ischemic stroke recurrence beyond a model incorporating clinical risk factors only.

Dual-energy CT (DECT) material decomposition techniques may better detect edema within cerebral infarcts than conventional non-contrast CT (NCCT). This study compared if Virtual Ischemia Maps (VIM) derived from non-contrast DECT of patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are superior to NCCT for ischemic core estimation, compared against reference-standard DWI-MRI. Only patients whose baseline ischemic core was most likely to remain stable on follow-up MRI were included, defined as those with excellent post-thrombectomy revascularization or no perfusion mismatch. Twenty-four consecutive AIS-LVO patients with baseline non-contrast DECT, CT perfusion (CTP), and DWI-MRI were analyzed. The primary outcome measure was agreement between volumetric manually segmented VIM, NCCT, and automatically segmented CTP estimates of the ischemic core relative to manually segmented DWI volumes. Volume agreement was assessed using Bland-Altman plots and comparison of CT to DWI volume ratios. DWI volumes were better approximated by VIM than NCCT (VIM/DWI ratio 0.68 ± 0.35 vs. NCCT/DWI ratio 0.34 ± 0.35; P < 0.001) or CTP (CTP/DWI ratio 0.45 ± 0.67; P < 0.001), and VIM best correlated with DWI (r VIM  = 0.90; r NCCT  = 0.75; r CTP  = 0.77; P < 0.001). Bland-Altman analyses indicated significantly greater agreement between DWI and VIM than NCCT core volumes (mean bias 0.60 [95%AI 0.39-0.82] vs. 0.20 [95%AI 0.11-0.30]). We conclude that DECT VIM estimates the ischemic core in AIS-LVO patients more accurately than NCCT.

Background: High activities of holmium-166 ( 166 Ho)-labeled microspheres are used for therapeutic radioembolization, ideally directly followed by SPECT imaging for dosimetry purposes. The resulting high-count rate potentially impacts dead time, affecting the image quality and dosimetric accuracy. This study assesses gamma camera performance and SPECT image quality at high 166 Ho activities of several GBq. To this purpose, the liver compartment, including two tumors, of an anthropomorphic phantom was filled with 166 Ho-chloride, with a tumor to non-tumorous liver activity concentration ratio of 10:1. Multiple SPECT/CT scans were acquired over a range of activities up to 2.7 GBq. Images were reconstructed using a commercially available protocol incorporating attenuation and scatter correction. Dead time effects were assessed from the observed count rate in the photopeak (81 keV, 15% width) and upper scatter (118 keV, 12% width) window. Post reconstruction, each image was scaled with an individual conversion factor to match the known total activity in the phantom at scanning time. The resulting activity concentration was measured in the tumors and non-tumorous liver. The image quality as a function of activity was assessed by a visual check of the absence of artifacts by a nuclear medicine physician. The apparent lung shunt fraction (nonzero due to scatter) was estimated on planar and SPECT images., Results: A 20% count loss due to dead time was observed around 0.7 GBq in the photopeak window. Independent of the count losses, the measured activity concentration was up to 100% of the real value for non-tumorous liver, when reconstructions were normalized to the known activity at scanning time. However, for tumor spheres, activity concentration recovery was ~80% at the lowest activity, decreasing with increasing activity in the phantom. Measured lung shunt fractions were relatively constant over the considered activity range., Conclusions: At high 166 Ho count rate, all images, visually assessed, presented no artifacts, even at considerable dead time losses. A quantitative evaluation revealed the possibility of reliable dosimetry within the healthy liver, as long as a post-reconstruction scaling to scanning activity is applied. Reliable tumor dosimetry, instead, remained hampered by the dead time.

Purpose: A compact and mobile hybrid c-arm scanner, capable of simultaneously acquiring nuclear and fluoroscopic projections and SPECT/CBCT, was developed to aid fluoroscopy-guided interventional procedures involving the administration of radionuclides (e.g. hepatic radioembolization). However, as in conventional SPECT/CT, the acquired nuclear images may be deteriorated by patient respiratory motion. We propose to perform compensation for respiratory motion by extracting the motion signal from fluoroscopic projections so that the nuclear counts can be gated into motion bins. The purpose of this study is to quantify the performance of this motion compensation technique with phantom experiments., Methods: Anthropomorphic phantom configurations that are representative of distributions obtained during the pre-treatment procedure of hepatic radioembolization were placed on a stage that translated with three different motion patterns. Fluoroscopic projections and nuclear counts were simultaneously acquired under planar and SPECT/CBCT imaging. The planar projections were visually assessed. The SPECT reconstructions were visually assessed and quantitatively assessed by calculating the activity recovery of the spherical inserts in the phantom., Results: The planar nuclear projections of the translating anthropomorphic phantom were blurry when no motion compensation was applied. With motion compensation, the nuclear projections became representative of the stationary phantom nuclear projection. Similar behavior was observed for the visual quality of SPECT reconstructions. The mean error of the activity recovery in the uncompensated SPECT reconstructions was 15.8% ± 0.9% for stable motion, 11.9% ± 0.9% for small variations, and 11.0% ± 0.9% for large variations. When applying motion compensation, the mean error decreased to 1.8% ± 1.6% for stable motion, 2.2% ± 1.5% for small variations, and 5.2% ± 2.5% for large variations., Conclusion: A compact and mobile hybrid c-arm scanner, capable of simultaneously acquiring nuclear and fluoroscopic projections, can perform compensation for respiratory motion. Such motion compensation results in sharper planar nuclear projections and increases the quantitative accuracy of the SPECT reconstructions.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Radioembolization is a treatment option for colorectal cancer (CRC) patients with inoperable, chemorefractory hepatic metastases. Personalized treatment requires established dose thresholds. Hence, the aim of this study was to explore the relationship between dose and effect (i.e., response and toxicity) in CRC patients treated with 166 Ho radioembolization. Methods: CRC patients treated in the HEPAR II and SIM studies were analyzed. Absorbed doses were estimated using the activity distribution on posttreatment 166 Ho SPECT/CT. Metabolic response was assessed using the change in total-lesion glycolysis on 18 F-FDG PET/CT between baseline and 3-mo follow-up. Toxicity between treatment and 3 mo was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5, and its relationship with parenchyma-absorbed dose was assessed using linear models. The relationship between tumor-absorbed dose and patient- and tumor-level response was analyzed using linear mixed models. Using a threshold of 100% sensitivity for response, the threshold for a minimal mean tumor-absorbed dose was determined and its impact on survival was assessed. Results: Forty patients were included. The median parenchyma-absorbed dose was 37 Gy (range, 12-55 Gy). New CTCAE grade 3 or higher clinical and laboratory toxicity was present in 8 and 7 patients, respectively. For any clinical toxicity (highest grade per patient), the mean difference in parenchymal dose (Gy) per step increase in CTCAE grade category was 5.75 (95% CI, 1.18-10.32). On a patient level, metabolic response was as follows: complete response, n = 1; partial response, n = 11; stable disease, n = 17; and progressive disease, n = 8. The mean tumor-absorbed dose was 84% higher in patients with complete or partial response than in patients with progressive disease (95% CI, 20%-180%). Survival for patients with a mean tumor-absorbed dose of more than 90 Gy was significantly better than for patients with a mean tumor-absorbed dose of less than 90 Gy (hazard ratio, 0.16; 95% CI, 0.06-0.511). Conclusion: A significant dose-response relationship in CRC patients treated with 166 Ho radioembolization was established, and a positive association between toxicity and parenchymal dose was found. For future patients, it is advocated to use a 166 Ho scout dose to select patients and yo personalize the administered activity, targeting a mean tumor-absorbed dose of more than 90 Gy and a parenchymal dose of less than 55 Gy., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Background and Aims: The pattern of intracranial internal carotid artery calcification (ICAC) has been identified as an effect modifier of endovascular treatment in patients with acute ischemic stroke, but it is unclear whether it modifies the effect of intravenous thrombolysis. The purpose of this study was to evaluate the association between intravenous thrombolysis and 90-day clinical outcome, follow-up infarct volume, intracranial hemorrhage and recanalization across different patterns of ICAC., Methods: Patients with acute ischemic stroke were selected from the Dutch acute stroke study, a prospective multicenter observational cohort study. ICAC pattern was determined on admission thin-slice non-contrast CT and categorized as absent, intimal, medial or indistinguishable. The primary outcome was the ordinal 90-day modified Rankin Scale. Other outcomes included follow-up infarct volume, intracranial hemorrhage, recanalization and collateral status. Associations were quantified with regression analyses and stratified by ICAC pattern., Results: Of 982 patients, 609 (62%) received intravenous thrombolysis and 381 (39%) had a 90-day modified Rankin Scale of 3-6. Intravenous thrombolysis was associated with a lower 90-day modified Rankin Scale in the group without ICAC (adjusted OR 0.3; 95%-CI 0.1-0.9) and in the group with a medial ICAC pattern (adjusted OR 0.5; 95%-CI 0.3-0.8), but not in the groups with intimal (adjusted OR 0.9; 95%-CI 0.5-1.5) or indistinguishable patterns (adjusted OR 0.6; 95%-CI 0.2-1.8). The associations between intravenous thrombolysis and follow-up infarct volume and intracranial hemorrhage were not significant for any of the ICAC pattern groups. Intravenous thrombolysis was only associated with recanalization in the group with a medial ICAC pattern (adjusted OR 3.5; 95%-CI 1.2-11.0). Compared to an intimal ICAC pattern, a medial ICAC pattern was associated with good collateral status (adjusted OR 2.6; 95%-CI 1.1-6.0)., Conclusions: Intravenous thrombolysis was significantly associated with favorable clinical outcome and successful recanalization in the group with a medial ICAC pattern, but not in the group with an intimal ICAC pattern., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Early infarcts are hard to diagnose on non-contrast head CT. Dual-energy CT (DECT) may potentially increase infarct differentiation. The optimal DECT settings for differentiation were identified and evaluated., Methods: One hundred and twenty-five consecutive patients who presented with suspected acute ischemic stroke (AIS) and underwent non-contrast DECT and subsequent DWI were retrospectively identified. The DWI was used as reference standard. First, virtual monochromatic images (VMI) of 25 patients were reconstructed from 40 to 140 keV and scored by two readers for acute infarct. Sensitivity, specificity, positive, and negative predictive values for infarct detection were compared and a subset of VMI energies were selected. Next, for a separate larger cohort of 100 suspected AIS patients, conventional non-contrast CT (NCT) and selected VMI were scored by two readers for the presence and location of infarct. The same statistics for infarct detection were calculated. Infarct location match was compared per vascular territory. Subgroup analyses were dichotomized by time from last-seen-well to CT imaging., Results: A total of 80-90 keV VMI were marginally more sensitive (36.3-37.3%) than NCT (32.4%; p > 0.680), with marginally higher specificity (92.2-94.4 vs 91.1%; p > 0.509) for infarct detection. Location match was superior for VMI compared with NCT (28.7-27.4 vs 19.5%; p < 0.010). Within 4.5 h from last-seen-well, 80 keV VMI more accurately detected infarct (58.0 vs 54.0%) and localized infarcts (27.1 vs 11.9%; p = 0.004) than NCT, whereas after 4.5 h, 90 keV VMI was more accurate (69.3 vs 66.3%)., Conclusion: Non-contrast 80-90 keV VMI best differentiates normal from infarcted brain parenchyma.

Objective: We compared 40- to 70-keV virtual monoenergetic to conventional computed tomography (CT) perfusion reconstructions with respect to quality of perfusion maps., Methods: Conventional CT perfusion (CTP) images were acquired at 80 kVp in 25 patients, and 40- to 70-keV images were acquired with a dual-layer CT at 120 kVp in 25 patients. First, time-attenuation-curve contrast-to-noise ratio was assessed. Second, the perfusion maps of both groups were qualitatively analyzed by observers. Last, the monoenergetic reconstruction with the highest quality was compared with the clinical standard 80-kVp CTP acquisitions., Results: Contrast-to-noise ratio was significantly better for 40 to 60 keV as compared with 70 keV and conventional images (P < 0.001). Visually, the difference between the blood volume maps among reconstructions was minimal. The 50-keV perfusion maps had the highest quality compared with the other monoenergetic and conventional maps (P < 0.002)., Conclusions: The quality of 50-keV CTP images is superior to the quality of conventional 80- and 120-kVp images., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: The restricted bore diameter of current simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) systems can be an impediment to achieving similar patient positioning during PET/MRI planning and radiotherapy. Our goal was to evaluate the B 1 transmit (B 1 + ) uniformity, B 1 + efficiency, and specific absorption rate (SAR) of a novel radiofrequency (RF) body coil design, in which RF shielded PET detectors were integrated with the specific aim of enabling a wide-bore PET/MRI system., Materials and Methods: We designed and constructed a wide-bore PET/MRI RF body coil to be integrated with a clinical MRI system. To increase its inner bore diameter, the PET detectors were positioned between the conductors and the RF shield of the RF body coil. Simulations and experiments with phantoms and human volunteers were performed to compare the B 1 + uniformity, B 1 + efficiency, and SAR between our design and the clinical body coil., Results: In the simulations, our design achieved nearly the same B 1 + field uniformity as the clinical body coil and an almost identical SAR distribution. The uniformity findings were confirmed by the physical experiments. The B 1 + efficiency was 38% lower compared to the clinical body coil., Conclusions: To achieve wide-bore PET/MRI, it is possible to integrate shielding for PET detectors between the body coil conductors and the RF shield without compromising MRI performance. Reduced B 1 + efficiency may be compensated by adding a second RF amplifier. This finding may facilitate the application of simultaneous whole-body PET/MRI in radiotherapy planning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier B.V. on behalf of European Society of Radiotherapy & Oncology.)

Objective: To compare assessment of collaterals by single-phase computed tomography (CT) angiography (CTA) and CT perfusion-derived 3-phase CTA, multiphase CTA and temporal maximum-intensity projection (tMIP) images to digital subtraction angiography (DSA), and relate collateral assessments to clinical outcome in patients with acute ischemic stroke., Methods: Consecutive acute ischemic stroke patients who underwent CT perfusion, CTA, and DSA before thrombectomy with occlusion of the internal carotid artery, the M1 or the M2 segments were included. Two observers assessed all CT images and one separate observer assessed DSA (reference standard) with static and dynamic (modified American Society of Interventional and Therapeutic Neuroradiology) collateral grading methods. Interobserver agreement and concordance were quantified with Cohen-weighted κ and concordance correlation coefficient, respectively. Imaging assessments were related to clinical outcome (modified Rankin Scale, ≤ 2)., Results: Interobserver agreement (n = 101) was 0.46 (tMIP), 0.58 (3-phase CTA), 0.67 (multiphase CTA), and 0.69 (single-phase CTA) for static assessments and 0.52 (3-phase CTA) and 0.54 (multiphase CTA) for dynamic assessments. Concordance correlation coefficient (n = 80) was 0.08 (3-phase CTA), 0.09 (single-phase CTA), and 0.23 (multiphase CTA) for static assessments and 0.10 (3-phase CTA) and 0.27 (multiphase CTA) for dynamic assessments. Higher static collateral scores on multiphase CTA (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7) and tMIP images (OR, 2.0; 95% CI, 1.1-3.4) were associated with modified Rankin Scale of 2 or less as were higher modified American Society of Interventional and Therapeutic Neuroradiology scores on 3-phase CTA (OR, 1.5; 95% CI, 1.1-2.2) and multiphase CTA (OR, 1.7; 95% CI, 1.1-2.6)., Conclusions: Concordance between assessments on CT and DSA was poor. Collateral status evaluated on 3-phase CTA and multiphase CTA, but not on DSA, was associated with clinical outcome.

Thrombus permeability determines blood flow through the occluding thrombus in acute ischemic stroke (AIS) patients. The quantification of thrombus permeability is challenging since it cannot be directly measured nor derived from radiological imaging data. As a proxy of thrombus permeability, thrombus perviousness has been introduced, which assesses the amount of contrast agent that has penetrated the thrombus on single-phase computed tomography angiography (CTA). We present a method to assess thrombus permeability rather than perviousness. We follow a three-step approach: (1) we propose a theoretical channel-like structure model describing the thrombus morphology. Using Darcy's law, we provide an analytical description of the permeability for this model. According to the channel-like model, permeability depends on the number of channels in the thrombus, the radius of the occluded artery, and the void fraction representing the volume available for the blood to flow; (2) we measure intra-thrombus blood flow and velocity on dynamic CTA; and (3) we combine the analytical model with the dynamic CTA measurements to estimate thrombus permeability. Analysis of dynamic CTA data from 49 AIS patients showed that the median blood velocity in the thrombus was 0.58 (IQR 0.26-1.35) cm/s. The median flow within the thrombus was 3.48 · 10 -3 (IQR 1.71 · 10 -3 -9.21 · 10 -3 ) ml/s. Thrombus permeability was of the order of 10 -3 -10 -5 mm 2 , depending on the number of channels in the thrombus. The channel-like thrombus model offers an intuitive way of modelling thrombus permeability, which can be of interest when studying the effect of thrombolytic drugs., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Interventional procedures involving radionuclides (e.g., radioembolization) would benefit from single-photon emission computed tomography (SPECT) performed in the intervention room because the activity distribution could be immediately visualized. We believe it might be possible to perform SPECT with the C-arm cone beam computed tomography (CBCT) scanner present in the intervention room by equipping the x-ray flat panel detector with a collimator. The purpose of this study is to demonstrate the approach and to investigate the achievable SPECT reconstruction quality., Methods: A proof-of-concept experiment was performed to evaluate the possibility of nuclear imaging with an x-ray flat panel detector. The experiment was digitally replicated to study the accuracy of the simulations. Three flat panel configurations (with standard hardware and reconstruction methodology, with sophisticated reconstruction methodology, and with expected future hardware) and a conventional gamma camera were evaluated. The Jaszczak and the NEMA IQ phantom (filled with 99m Tc) were simulated and assessed on resolution and contrast-to-noise ratio (CNR)., Results: The proof-of-concept experiment demonstrated that nuclear images could be obtained from the flat panel detector. The simulation of the same configuration demonstrated that simulations could accurately predict the flat panel detector response. The CNR of the 37 mm sphere in the NEMA IQ phantom was 22.8 ± 1.2 for the gamma camera reconstructions, while it was 11.3 ± 0.7 for the standard flat panel detector. With sophisticated reconstruction methodology, the CNR improved to 13.5 ± 1.4. The CNR can be expected to advance to 18.1 ± 1.3 for future flat panel detectors., Conclusions: The x-ray flat panel detector of a CBCT scanner might be used to perform nuclear imaging. The SPECT reconstruction quality will be lower than that achieved by a conventional gamma camera. The flat panel detector approach could, however, be useful in providing a cost-effective alternative to the purchase of a mobile SPECT scanner for enabling interventional scanning., (© 2020 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Myocardial perfusion imaging is a commonly performed SPECT protocol and hence it would be beneficial if its scan duration could be shortened. For traditional gamma cameras, two developments have separately shown to allow for a shortened scan duration: (i) reconstructing with Monte Carlo-based scatter correction instead of dual-energy window scatter correction and (ii) acquiring projections with the SMARTZOOM collimator instead of a parallel-hole collimator. This study investigates which reduction in scan duration can be achieved when both methods are combined in a single system., Results: The SMARTZOOM collimator was implemented in a Monte Carlo-based reconstruction package and the implementation was validated through image quality phantom experiments. The potential for scan duration reduction was evaluated with a phantom configuration that is realistic for myocardial perfusion imaging. The original reconstruction quality was achieved in 76 ± 8% of the original scan duration when switching from dual-energy window scatter correction to Monte Carlo-based scatter correction. The original reconstruction quality was achieved in 56 ± 13% of the original scan duration when switching from the parallel-hole to the SMARTZOOM collimator. After combining both methods in a single system, the original reconstruction quality was achieved in 34 ± 7% of the original scan duration., Conclusions: Monte Carlo-based scatter correction combined with the SMARTZOOM collimator can further decrease the scan duration in myocardial perfusion imaging.

Purpose: It may be challenging to select the optimal scan duration for single-photon emission computed tomography (SPECT) protocols because the activity distribution characteristics can differ in every scan. Using simulations and experiments, we investigated whether the scan duration can be optimized for every scan separately by evaluating the activity distribution during scanning. We refer to this as adaptive scanning., Methods: The feasibility of adaptive scanning was evaluated for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization, in which 99m Tc-labeled macroaggregated albumin ( 99m Tc-MAA) is injected into the liver. We simulated fast 1-min detector rotations and updated the reconstruction with the newly collected counts after every rotation. The scan was terminated when one of the two criteria was met: (a) when the mask difference of the detected extrahepatic deposition between two consecutive rotations was lower than 5%; or (b) when the reconstructed extrahepatic activity was negligible with respect to the total reconstructed activity (<0.075%). The performance of adaptive scanning was evaluated using a digital phantom with various activity distributions, a physical phantom experiment, and simulations based on 129 patient activity distributions., Results: The digital phantom data showed that the scan termination times substantially depended on the activity distribution characteristics. The experimental phantom data showed the feasibility of adaptive scanning with physical scanner measurements and illustrated that fast detector motion was not limiting the adaptive scanning performance. The patient data showed a large spread in the scan terminations times. By adaptive scanning, the mean scan duration of the patient distributions was shortened from 20 min (current clinical protocol) to 4.8 ± 0.2 min. The detection accuracy of extrahepatic depositions was unaffected and the mean difference in the extrahepatic deposition masks (compared with the 20-min scan) was only 7.0 ± 1.0%., Conclusion: Our study suggests that the SPECT scan duration can be personalized by assessing the activity distribution characteristics during scanning for the detection of extrahepatic depositions in the pretreatment procedure of radioembolization. The adaptive scanning approach might also be of benefit for other SPECT protocols, as long as a measure of interest is available for optimization., (© 2020 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)