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Purpose: Intraoperative radiotherapy (IORT) has become a viable treatment option for resectable brain metastases (BMs). As data on local control and radiation necrosis rates are maturing, we focus on meaningful secondary endpoints such as time to next treatment (TTNT), duration of postoperative corticosteroid treatment, and in-hospital time., Methods: Patients prospectively recruited within an IORT study registry between November 2020 and June 2023 were compared with consecutive patients receiving adjuvant stereotactic radiotherapy (SRT) of the resection cavity within the same time frame. TTNT was defined as the number of days between BM resection and start of the next extracranial oncological therapy (systemic treatment, surgery, or radiotherapy) for each of the groups., Results: Of 95 BM patients screened, IORT was feasible in 84 cases (88%) and ultimately performed in 64 (67%). The control collective consisted of 53 SRT patients. There were no relevant differences in clinical baseline features. Mean TTNT (range) was 36 (9 - 94) days for IORT patients versus 52 (11 - 126) days for SRT patients (p = 0.01). Mean duration of postoperative corticosteroid treatment was similar (8 days; p = 0.83), as was mean postoperative in-hospital time (11 versus 12 days; p = 0.97). Mean total in-hospital time for BM treatment (in- and out-patient days) was 11 days for IORT versus 19 days for SRT patients (p < 0.001)., Conclusion: IORT for BMs results in faster completion of interdisciplinary treatment when compared to adjuvant SRT, without increasing corticosteroid intake or prolonging in-hospital times. A randomised phase III trial will determine the clinical effects of shorter TTNT., (© 2023. The Author(s).)

Purpose: Intraoperative radiation therapy (IORT) is an emerging alternative to adjuvant stereotactic external beam radiation therapy (EBRT) following resection of brain metastases (BM). Advantages of IORT include an instant prevention of tumor regrowth, optimized dose-sparing of adjacent healthy brain tissue and immediate completion of BM treatment, allowing an earlier admission to subsequent systemic treatments. However, prospective outcome data are limited. We sought to assess long-term outcome of IORT in comparison to EBRT., Methods: A total of 35 consecutive patients, prospectively recruited within a study registry, who received IORT following BM resection at a single neuro-oncological center were evaluated for radiation necrosis (RN) incidence rates, local control rates (LCR), distant brain progression (DBP) and overall survival (OS) as long-term outcome parameters. The 1 year-estimated OS and survival rates were compared in a balanced comparative matched-pair analysis to those of our institutional database, encompassing 388 consecutive patients who underwent adjuvant EBRT after BM resection., Results: The median IORT dose was 30 Gy prescribed to the applicator surface. A 2.9% RN rate was observed. The estimated 1 year-LCR was 97.1% and the 1 year-DBP-free survival 73.5%. Median time to DBP was 6.4 (range 1.7-24) months in the subgroup of patients experiencing intracerebral progression. The median OS was 17.5 (0.5-not reached) months with a 1 year-survival rate of 61.3%, which did not not significantly differ from the comparative cohort (p = 0.55 and p = 0.82, respectively)., Conclusion: IORT is a safe and effective fast-track approach following BM resection, with comparable long-term outcomes as adjuvant EBRT., (© 2023. The Author(s).)

Purpose: To evaluate the clinical applicability of a prototype virtual non-contrast (VNC) reconstruction algorithm based on coronary CT angiography (cCTA) to assess calcified coronary plaques by calcium scoring (CACS)., Methods: Eighty consecutive patients suspected of coronary artery disease were retrospectively included. All patients underwent a cardiac CT using a dual-layer spectral-detector CT system. The standardized acquisition protocol included unenhanced CACS and cCTA. Datasets were acquired using 120 keV. VNC-reconstructions were calculated from the cCTA images at 2.5 mm (VNC group 1), 2.5 of 0.9 mm (group 2), and 0.9 mm (group 3) slice thickness. We compared the Agatston score and Coronary Artery Calcium Data and Reporting System (CAC-DRS) of all VNC reconstructions with the true non-contrast (TNC)-dataset as the gold standard., Results: In total, 73 patients were evaluated. Fifty patients (68.5 %) had a CACS > 0 based on TNC. We found a significant difference in the Agatston score comparing all VNC-reconstructions (1: 1.35, 2: 3.7, 3: 10.4) with the TNC dataset (3.8) (p < 0.001). Correlation analysis of the datasets showed an excellent correlation of the TNC results with the different VNC-reconstructions (r = 0.904-0.974, p < 0.001) with a slope of 1.89-2.53. Mean differences and limits of agreement by Bland-Altman analysis between TNC and group 1 were 83 and -196 to 362, respectively. By using the VNC-reconstructions, in group 1 23 patients (31.5 %), in group 2 10 (13.7 %), and in group 3 23 (31.5 %) were reclassified according to CAC-DRS compared to TNC. Classification according to CAC-DRS revealed a significant difference between TNC and group 1 (p = 0.024) and no significance compared to groups 2 and 3 (p = 0.670 and 0.273)., Conclusion: The investigated VNC reconstruction algorithm of routine cCTA allows the detection and evaluation of coronary calcium burden without the requirement for an additional acquisition of an unenhanced CT scan for CACS and, therefore, a reduction of radiation exposure., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [EL and GP are employees of Philips Healthcare. The other authors have no conflict of interest to disclose.], (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intraoperative radiotherapy (IORT) of the operative cavity for surgically treated brain metastasis (BM) has gained increasing prominence with respect to improved local tumor control. However, IORT immediately performed at the time of surgery might be associated with increased levels of perioperative adverse events (PAEs). In the present study, we performed safety metric profiling in patients who had undergone surgery for BM with and without IORT in order to comparatively analyze feasibility of IORT as an adjuvant radiation approach. Between November 2020 and October 2021, 35 patients were surgically treated for BM with IORT at our neuro-oncological center. Perioperative complication profiles were collected in a prospective observational cohort study by means of patient safety indicators (PSIs), hospital-acquired conditions (HACs), and specific cranial-surgery-related complications (CSCs) as high-standard quality metric tools and compared to those of an institutional cohort of 388 patients with BM resection without IORT in a balanced comparative matched-pair analysis. Overall, 4 out of 35 patients (11%) with IORT in the course BM resection suffered from PAEs, accounting for 3 PSIs (9%) and 1 HAC (3%). Balanced matched-pair analysis did not reveal significant differences in the perioperative complication profiles between the cohorts of patients with and without IORT ( p = 0.44). Thirty-day mortality rates were 6% for patients with IORT versus 8% for patients without IORT ( p = 0.73). The present study demonstrates that IORT constitutes a safe and clinically feasible adjuvant treatment modality in patients undergoing surgical resection of BM.

Purpose/objectives: To perform a dosimetric comparison between kilovoltage intraoperative radiotherapy (IORT) and stereotactic radiosurgery (SRS) simulating both deep-inspiration breath-hold (DIBH) and free-breathing (FB) modalities for patients with liver metastases., Methods/materials: Diagnostic computed tomographies (CT) of patients carrying one or two lesions <4 cm and who underwent surgery were retrospectively screened and randomly selected for the study. For DIBH-SRS, a gross target volume (GTV) plus planning target volume (PTV) were delineated. For FB-SRS, a GTV plus an internal target volume (ITV) and PTV were defined. Accounting for the maximal GTV diameters, a modified GTV (GTV-IORT) was expanded circumferentially to simulate a resection cavity. The best suitable round-applicator size was thereafter selected. All treatment plans were calculated homogeneously to deliver 40 Gy. Doses delivered to organs at risk (OAR) and target volumes were compared for IORT vs. both SRS modalities., Results: Eight patients encompassing 10 lesions were included in the study. The mean liver volume was 2,050.97 cm 3 (SD, 650.82), and the mean GTV volume was 12.23 cm 3 (SD, 12.62). As for target structures, GTV-IORT [19.44 cm 3 (SD, 17.26)] were significantly smaller than both PTV DIBH-SRS [30.74 cm 3 (SD, 24.64), p = 0.002] and PTV FB-SRS [75.82 cm 3 (SD, 45.65), p = 0.002]. The median applicator size was 3 cm (1.5-4.5), and the mean IORT simulated delivery time was 45.45 min (SD, 19.88). All constraints were met in all modalities. Liver V 9.1 showed significantly smaller volumes with IORT [63.39 cm 3 (SD, 35.67)] when compared to DIBH-SRS [150.12 cm 3 (SD, 81.43), p = 0.002] or FB-SRS [306.13 cm 3 (SD, 128.75), p = 0.002]. No other statistical or dosimetrically relevant difference was observed for stomach, spinal cord, or biliary tract. Mean IORT D 90 was 85.3% (SD, 6.05), whereas D 95 for DIBH-SRS and FB-SRS were 99.03% (SD, 1.71; p = 0.042) and 98.04% (SD, 3.46; p = 0.036), respectively., Conclusion: Kilovoltage IORT bears the potential as novel add-on treatment for resectable liver metastases, significantly reducing healthy liver exposure to radiation in comparison to SRS. Prospective clinical evidence is required to confirm this hypothesis., Competing Interests: DS has stocks from AstraZeneca GmbH. MG-C received travel expenses and honoraria from Bristol-Myers Squibb, Roche, MSD, IPSEN, Eisai, Amgen, and Servier not related to this work. FG received research grants and travel expenses from ELEKTA AB; grants, stocks, travel expenses, and honoraria from NOXXON Pharma AG; research grants, travel expenses and honoraria from Carl Zeiss Meditec AG; travel expenses and honoraria from Bristol-Myers Squibb, Roche Pharma AG, MSD Sharp and Dohme GmbH and AstraZeneca GmbH; non-financial support from Oncare GmbH and Opasca GmbH, not related to this work. LS GS received personal fees from Carl Zeiss Meditec AG, personal fees from Roche Pharma AG, personal fees from MedWave Clinical Research BV, and travels expenses from Guerbet GmbH. 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 © 2021 Scafa, Muedder, Holz, Koch, Nour, Garbe, Gonzalez-Carmona, Feldmann, Vilz, Köksal, Giordano, Schmeel and Sarria.)

Purpose: To simulate and analyze the dosimetric differences of intraoperative radiotherapy (IORT) or pre-operative single-fraction stereotactic radiosurgery (SRS) in addition to post-operative external beam radiotherapy (EBRT) in Glioblastoma (GB)., Methods: Imaging series of previously treated patients with adjuvant radiochemotherapy were analyzed. For SRS target definition, pre-operative MRIs were co-registered to planning CT scans and a pre-operative T1-weighted gross target volume (GTV) plus a 2-mm planning target volume (PTV) were created. For IORT, a modified (m)GTV was expanded from the pre-operative volume, in order to mimic a round cavity as during IORT. Dose prescription was 20 Gy, homogeneously planned for SRS and calculated at the surface for IORT, to cover 99% and 90% of the volumes, respectively. For tumors > 2cm in maximum diameter, a 15 Gy dose was prescribed. Plan assessment was performed after calculating the 2-Gy equivalent doses (EQD2) for both boost modalities and including them into the EBRT plan. Main points of interest encompass differences in target coverage, brain volume receiving 12 Gy or more (V 12 ), and doses to various organs-at-risk (OARs)., Results: Seventeen pre-delivered treatment plans were included in the study. The mean GTV was 21.72 cm 3 (SD ± 19.36) and mGTV 29.64 cm 3 (SD ± 25.64). The mean EBRT and SRS PTV were 254.09 (SD ± 80.0) and 36.20 cm 3 (SD ± 31.48), respectively. Eight SRS plans were calculated to 15 Gy according to larger tumor sizes, while all IORT plans to 20 Gy. The mean EBRT D 95 was 97.13% (SD ± 3.48) the SRS D 99 99.91% (SD ± 0.35) and IORT D 90 83.59% (SD ± 3.55). Accounting for only-boost approaches, the brain V 12 was 49.68 cm 3 (SD ± 26.70) and 16.94 cm 3 (SD ± 13.33) (p<0.001) for SRS and IORT, respectively. After adding EBRT results respectively to SRS and IORT doses, significant lower doses were found in the latter for mean D max of chiasma (p=0.01), left optic nerve (p=0.023), right (p=0.008) and left retina (p<0.001). No significant differences were obtained for brainstem and cochleae., Conclusion: Dose escalation for Glioblastoma using IORT results in lower OAR exposure as conventional SRS., Competing Interests: GS: personal fees from Carl Zeiss Meditec AG and personal fees from Roche Pharma AG, not related to this work. FG: research grants and travel expenses from ELEKTA AB; grants, stocks, travel expenses and honoraria from NOXXON Pharma AG; research grants, travel expenses and honoraria from Carl Zeiss Meditec AG; travel expenses and honoraria from Bristol-Myers Squibb, Roche Pharma AG, MSD Sharp and Dohme GmbH and AstraZeneca GmbH; non-financial support from Oncare GmbH and Opasca GmbH, not related to this work. 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 © 2021 Sarria, Smalec, Muedder, Holz, Scafa, Koch, Garbe, Schneider, Hamed, Vatter, Herrlinger, Giordano and Schmeel.)

The inability to assess and measure changes to the airway smooth muscle (ASM) in vivo is a major challenge to evaluating asthma and its clinical outcomes. Bronchial thermoplasty (BT) is a therapy for asthma that aims to reduce the severity of excessive bronchoconstriction by ablating ASM. Although multiple long-term clinical studies of BT have produced encouraging results, the outcomes of BT treatment in practice have been variable, and questions remain regarding the selection of patients. Previously, we have demonstrated an imaging platform called orientation-resolved optical coherence tomography that can assess ASM endoscopically using an imaging catheter compatible with bronchoscopy. In this work, we present results obtained from a longitudinal BT study performed using a canine model ( n = 8) and with the goal of investigating the use of orientation-resolved optical coherence tomography (OR-OCT) for measuring the effects of BT on ASM. We demonstrate that we are capable of accurately assessing ASM both before and in the weeks following the BT procedure using blinded matching to histological samples stained with Masson's trichrome ( P < 0.0001, r 2 = 0.79). Analysis of volumetric ASM distributions revealed significant decreases in ASM in treated airways (average cross-sectional ASM area: 0.245 ± 0.145 mm 2 pre-BT and 0.166 ± 0.112 mm 2 6 wk following BT). These results demonstrate that OR-OCT can provide clinicians with the feedback necessary to better evaluate ASM and its response to BT, and may potentially play an important role in phenotyping asthma and predicting which patients are most likely to respond to BT treatment. NEW & NOTEWORTHY The inability to assess ASM in vivo is a significant hurdle in advancing our understanding of airway diseases such as asthma, as well as evaluating potential treatments and therapies. In this study, we demonstrate that endoscopic OR-OCT can be used to accurately measure changes to ASM structure following BT. Our results demonstrate how this technology could occupy an important role in asthma treatments targeting ASM.

Dual-energy CT allows for the reconstruction of virtual non-contrast (VNC) images. VNC images have the potential to replace true non-contrast scans in various clinical applications. This study investigated the quantitative accuracy of VNC attenuation images considering different parameters for acquisition and reconstruction. An abdomen phantom with 7 different tissue types (different combinations of 3 base materials and 5 iodine concentrations) was scanned using a spectral detector CT (SDCT). Different phantom sizes (S, M, L), volume computed tomography dose indices (CTDIvol 10, 15, 20 mGy), kernel settings (soft, standard, sharp), and denoising levels (low, medium, high) were tested. Conventional and VNC images were reconstructed and analyzed based on regions of interest (ROI). Mean and standard deviation were recorded and differences in attenuation between corresponding base materials and VNC was calculated (VNCerror). Statistic analysis included ANOVA, Wilcoxon test and multivariate regression analysis. Overall, the VNC error was - 1.4 ± 6.1 HU. While radiation dose, kernel setting, and denoising level did not influence VNC error significantly, phantom size, iodine content and base material had a significant effect (e.g. S vs. M: - 1.2 ± 4.9 HU vs. - 2.1 ± 6.0 HU; 0.0 mg/ml vs. 5.0 mg/ml: - 4.0 ± 3.5 HU vs. 5.1 ± 5.0 HU and 35-HU-base vs. 54-HU-base: - 3.5 ± 4.4 HU vs. 0.7 ± 6.5; all p ≤ 0.05). The overall accuracy of VNC images from SDCT is high and independent from dose, kernel, and denoising settings; however, shows a dependency on patient size, base material, and iodine content; particularly the latter results in small, yet, noticeable differences in VNC attenuation.

Numerous methods for artifact quantification in computed tomography (CT) imaging have been suggested. This study evaluated their utility with regards to correspondence with visual artifact perception and reproducibility. Two titanium rods (5 and 10 mm) were examined with 25 different scanning- and image-reconstruction parameters resulting in different types and extents of artifacts. Four radiologists evaluated every image against each other using an in-house developed software. Rating was repeated two times (2,400 comparisons = 2 times × 4 readers × 300 comparisons). Rankings were combined to obtain a reference ranking. Proposed approaches for artifact quantification include manual measurement of attenuation, standard deviation and noise and sophisticated algorithm-based approaches within the image- and frequency-domain. Two radiologists conducted manual measurements twice while the aforementioned algorithms were implemented within the Matlab-Environment allowing for automated image analysis. The reference ranking was compared to all aforementioned methods for artifact quantification to identify suited approaches. Besides visual analysis, Kappa-statistics and intraclass correlation coefficients (ICC) were used. Intra- and Inter-reader agreements of visual artifact perception were excellent (ICC 0.85-0.92). No quantitative method was able to represent the exact ranking of visually perceived artifacts; however, ICC for manual measurements were low (ICC 0.25-0.97). The method that showed best correspondence and reproducibility used a Fourier-transformed linear ROI and lower-end frequency bins. Automated measurements of artifact extent should be preferred over manual measurements as the latter show a limited reproducibility. One method that allows for automated quantification of such artefacts is made available as an electronic supplement., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims.2020.04.03). NGH reports grants and personal fees from Philips Healthcare, outside the submitted work. BE reports personal fees from BioInvision, Inc., outside the submitted work. DPS reports personal fees from Cook Medical, personal fees from mediaire GmbH, outside the submitted work. JAH reports grants from Philips, outside the submitted work. DM reports personal fees from Philips Healthcare, outside the submitted work. The other authors have no conflicts of interest to declare., (2020 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: The aim of the study was to evaluate the effect of slice thickness, iterative reconstruction (IR) algorithm, and kernel selection on measurement accuracy and interobserver variability for semiautomated renal cortex volumetry (RCV) with multislice computed tomography (CT)., Methods: Ten patients (62.4 ± 17.2 years) undergoing abdominal biphasic multislice computed tomography were enrolled in this retrospective study. Computed tomography data sets were reconstructed at 1-, 2-, and 5-mm slice thickness with 2 different IR algorithms (iDose, IMRST) and 2 different kernels (IMRS and IMRR) (Philips, the Netherlands). Two readers independently performed semiautomated RCV for each reconstructed data set to calculate left kidney volume (LKV) and split renal function (SRF). Statistics were calculated using analysis of variance with Geisser-Greenhouse correction, followed by Tukey multiple comparisons post hoc test. Statistical significance was defined as P ≤ 0.05., Results: Semiautomated RCV of 120 data sets (240 kidneys) was successfully performed by both readers. Semiautomated RCV provides comparable results for LKV and SRF with 3 different slice thicknesses, 2 different IR algorithms, and 2 different kernels. Only the 1-mm slice thickness showed significant differences for LKV between IMRR and IMRS (P = 0.02, mean difference = 4.28 bb) and IMRST versus IMRS (P = 0.02, mean difference = 4.68 cm) for reader 2. Interobserver variability was low between both readers irrespective of slice thickness and reconstruction algorithm (0.82 ≥ P ≥ 0.99)., Conclusions: Semiautomated RCV measurements of LKV and SRF are independent of slice thickness, IR algorithm, and kernel selection. These findings suggest that comparisons between studies using different slice thicknesses and reconstruction algorithms for RCV are valid.

Background and Objective: In vivo evaluation of the microstructural differences between asthmatic and non-asthmatic airways and their functional consequences is relevant to understanding and, potentially, treating asthma. In this study, we use endobronchial optical coherence tomography to investigate how allergic airways with asthma differ from allergic non-asthmatic airways in baseline microstructure and in response to allergen challenge., Methods: A total of 45 subjects completed the study, including 20 allergic, mildly asthmatic individuals, 22 non-asthmatic allergic controls and 3 healthy controls. A 3-cm airway segment in the right middle and right upper lobe were imaged in each subject immediately before and 24 h following segmental allergen challenge to the right middle lobe. Relationships between optical airway measurements (epithelial and mucosal thicknesses, mucosal buckling and mucus) and airway obstruction (FEV 1 /FVC (forced expiratory volume in 1 s/forced vital capacity) and FEV 1 % (FEV 1 as a percentage of predictive value)) were investigated., Results: Significant increases at baseline and in response to allergen were observed for all four of our imaging metrics in the asthmatic airways compared to the non-asthmatic airways. Epithelial thickness and mucosal buckling exhibited a significant relationship to FEV 1 /FVC in the asthmatic group., Conclusion: Simultaneous assessments of airway microstructure, buckling and mucus revealed both structural and functional differences between the mildly asthmatic and control groups, with airway buckling seeming to be the most relevant factor. The results of this study demonstrate that a comprehensive, microstructural approach to assessing the airways may be important in future asthma studies as well as in the monitoring and treatment of asthma., (© 2019 Asian Pacific Society of Respirology.)

Objective: To evaluate feasibility and diagnostic performance of multi-level calcium suppression in spectral detector computed tomography (SDCT) for assessment of bone metastasis., Materials and Methods: Retrospective IRB-approved study on 21 patients who underwent SDCT (120 kV, reference mAs 116) and MRI. Thoracic and lumbar vertebrae (n = 357) were included and categorized as normal (n = 133) or metastatic (n = 203) based on MRI (STIR, T1w, ±contrast). The multi-level virtual non-calcium (VNCa) algorithm computes dynamic soft tissue/calcium pairs allowing for computation of different suppression index levels to address inter-individual variance of prevalent calcium composition weights. We computed images with low, medium, and high calcium suppression indices and compared them with conventional images (VNCa&#95;low/med/high and conventional images (CI)). For quantitative image analysis, regions of interest were placed in normal and metastatic bone. Two readers reviewed the datasets independently in multiple sessions. They determined the presence of vertebral metastases on a per vertebra basis using a binary scale. Statistic assessment was performed using ANOVA with Tukey HSD, Student's T test, and ROC analysis., Results: Attenuation of both normal and metastatic bone was lower in VNCa images than that in conventional images (e.g., CI/VNCa&#95;low, - 46.3 to 238.8 HU/343.3-60.2 HU; p ≤ 0.05). VNCa&#95;low+med improved separation of normal and metastatic bone in ROC analysis (AUC, CI/VNCa&#95;low/VNCa&#95;med = 0.74/0.95/0.98; p ≤ 0.05). In subjective analysis, both sensitivity and specificity were clearly improved in VNCa&#95;low as compared with CI (0.85/0.84 versus 0.78/0.82). Readers showed a good inter-rater reliability (kappa = 0.65)., Conclusions: Multi-level VNCa reconstructed from SDCT improve quantitative separation of normal and metastatic bone and subjective determination of bone metastases when using low to intermediate calcium suppression indices., Key Points: • Spectral detector CT allows for multi-level calcium suppression in CT images and low and medium calcium suppression indices improved separation of normal and metastatic bone. • Thus, multi-level calcium suppression allows to optimize image contrast in regard to dedicated pathologies. • Low-level virtual non-calcium images (index 25-50) improved diagnostic performance regarding detection of metastasis.

Objective: To comprehensively assess precision, reproducibility, and repeatability of iodine maps from spectral detector CT (SDCT) in a phantom and in patients with repetitive examination of the abdomen., Methods: Seventy-seven patients who underwent examination two (n = 52) or three (n = 25) times according to clinical indications were included in this IRB-approved, retrospective study. The anthropomorphic liver phantom and all patients were scanned with a standardized protocol (SSDE in patients 15.8 mGy). In patients, i.v. contrast was administered and portal venous images were acquired using bolus-tracking technique. The phantom was scanned three times at three time points; in one acquisition, image reconstruction was repeated three times. Region of interest (ROI) were placed automatically (phantom) or manually (patients) in the liver parenchyma (mimic) and the portal vein; attenuation in conventional images (CI [HU]) and iodine map concentrations (IM [mg/ml]) were recorded. The coefficient of variation (CV [%]) was used to compare between repetitive acquisitions. If present, additional ROI were placed in cysts (n = 29) and hemangioma (n = 29)., Results: Differences throughout all phantom examinations were < 2%. In patients, differences between two examinations were higher (CV for CI/IM: portal vein, 2.5%/3.2%; liver parenchyma, -0.5%/-3.0% for CI/IM). In 80% of patients, these differences were within a ± 20% limit. Differences in benign liver lesions were even higher (68% and 38%, for CI and IM, respectively)., Conclusions: Iodine maps from SDCT allow for reliable quantification of iodine content in phantoms; while in patients, rather large differences between repetitive examinations are likely due to differences in biological distribution. This underlines the need for careful clinical interpretation and further protocol optimization., Key Points: • Spectral detector computed tomography allows for reliable quantification of iodine in phantoms. • In patients, the offset between repetitive examinations varies by 20%, likely due to differences in biological distribution. • Clinically, iodine maps should be interpreted with caution and should take the intra-individual variability of iodine distribution over time into account.

Purpose: To evaluate calcium suppressed images (CaSupp) in dual-layer detector computed tomography (DLCT) for the detection of bone marrow edema (BME) in vertebral fractures., Materials and Methods: The retrospective study was approved by the institutional review board. 34 patients with synchronous DLCT and MRI, who were diagnosed with one or more acute vertebral fractures, were included. MRI were systematically analyzed as reference standard. Two blinded and independent readers evaluated CaSupp for vertebral BME. Additionally, both readers determined the optimal calcium suppression indices (CaSupp-I) for visualization of BME in consensus and correlated the CaSupp-I with parallel measurement of trabecular density as surrogate parameter for bone mineral density. ROI-based measurements of the contrast-to-noise ratios (CNR) were also conducted. Interrater agreement was determined by kappa-statistics. CNR were analyzed using Wilcoxon signed rank test., Results: Fifty-seven acute fractured vertebrae out of 383 vertebrae (14.9%) were found. CaSupp yielded an average sensitivity of 87% and specificity of 99%, a positive predictive value of 95%, a negative predictive value of 98% and an accuracy of 97% for the detection of fracture-associated edema. Interrater agreement was excellent (kappa 0.91). Increase in CNR of BME correlated with increasing CaSupp-I. Edema adjacent to the cortical endplates was better visualized using CaSupp-I of 70 and 80, while extensive edema was better visualized using a CaSupp-I of 90 and 100 (chi2 < 0.0001). No correlation between optimal CaSupp-I and trabecular density was found (p > 0.2)., Conclusion: CaSupp reconstructed from DLCT enable visualization and detection of BME in traumatic fractured vertebrae with high diagnostic accuracy using CaSupp-I of 70-100., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: The aim of this study was to investigate the feasibility of kidney stone composition analysis using spectral detector computed tomography scanner (SDCT) with normal- and low-dose imaging protocols., Methods: A total of 154 stones harvested from nephrolithotripsy or nephrolithotomy with a known monocrystalline composition as determined by infrared spectroscopy were examined in a nonanthropomorphic phantom on an SDCT (IQon, Philips, Best, the Netherlands). Imaging was performed with 120 kVp and (a) 40 mAs and (b) 200 mAs, resulting in a computed tomography dose index (CTDIvol) of 2 and 10 mGy, respectively. Besides conventional CT images (CIs), SDCT enables reconstruction of virtual monoenergetic images (40-200 keV). Spectral coefficient images were calculated by performing a voxel-by-voxel combination of 40 and 200 keV images (Matlab R2017b, Mathworks Inc). All stones were semiautomatically 3D-segmented on CI using a threshold-based algorithm implemented in an offline DICOM viewer. Statistical assessment was performed using Steel-Dwass method to adjust for multiple comparisons., Results: Ca-phosphate (n = 22), Ca-oxalate (n = 82), cysteine (n = 20), struvite (n = 3), uric acid (n = 18), and xanthine stones (n = 9) were included in the analysis. Stone diameter ranged from 3.0 to 13.5 mm. On CI, attenuation differed significantly between calcific and noncalcific stones only (P ≤ 0.05), the spectral coefficient differed significantly between (//): Ca-oxalate//Ca-phosphate//cystine//struvite//uric acid//xanthine in 10 mGy protocol (all P ≤ 0.05). The same results were found for the 2 mGy-protocol, except that differentiation of Ca-oxalate and Ca-phosphate as well as uric acid and xanthine was not possible (P ≥ 0.05)., Conclusions: Spectral detector CT allows for differentiation of kidney stones using semi-automatic segmentation and advanced image post-processing, even in low-dose imaging protocols.

Objectives: Evaluation of imaging performance across dual-energy CT (DECT) platforms, including dual-layer CT (DLCT), rapid-kVp-switching CT (KVSCT) and dual-source CT (DSCT)., Methods: A semi-anthropomorphic abdomen phantom was imaged on these DECT systems. Scans were repeated three times for CTDIvol levels of 10 mGy, 20 mGy, 30 mGy and different fat-simulating extension rings. Over the available range of virtual-monoenergetic images (VMI), noise as well as quantitative accuracy of hounsfield units (HU) and iodine concentrations were evaluated., Results: For all VMI levels, HU values could be determined with high accuracy compared to theoretical values. For KVSCT and DSCT, a noise increase was observed towards lower VMI levels. A patient-size dependent increase in the uncertainty of quantitative iodine concentrations is observed for all platforms. For a medium patient size the iodine concentration root-mean-square deviation at 20 mGy is 0.17 mg/ml (DLCT), 0.30 mg/ml (KVSCT) and 0.77mg/ml (DSCT)., Conclusion: Noticeable performance differences are observed between investigated DECT systems. Iodine concentrations and VMI HUs are accurately determined across all DECT systems. KVSCT and DLCT deliver slightly more accurate iodine concentration values than DSCT for investigated scenarios. In DLCT, low-noise and high-image contrast at low VMI levels may help to increase diagnostic information in abdominal CT., Key Points: • Current dual-energy CT platforms provide accurate, reliable quantitative information. • Dual-energy CT cross-platform evaluation revealed noticeable performance differences between different systems. • Dual-layer CT offers constant noise levels over the complete energy range.

Background: Directional deep brain stimulation (DBS) allows steering the stimulation in an axial direction which offers greater flexibility in programming. However, accurate anatomical visualization of the lead orientation is required for interpreting the observed stimulation effects and to guide programming., Objectives: In this study we aimed to develop and test an accurate and robust algorithm for determining the orientation of segmented electrodes based on standard postoperative CT imaging used in DBS., Methods: Orientation angles of directional leads (CartesiaTM; Boston Scientific, Marlborough, MA, USA) were determined using CT imaging. Therefore, a sequential algorithm was developed that quantitatively compares the similarity of the observed CT artifacts with calculated artifact patterns based on the lead's orientation marker and a geometric model of the segmented electrodes. Measurements of seven ground truth phantoms and three leads with 60 different configurations of lead implantation and orientation angles were analyzed for validation., Results: The accuracy of the determined electrode orientation angles was -0.6 ± 1.5° (range: -5.4 to 4.2°). This accuracy proved to be sufficiently high to resolve even subtle differences between individual leads., Conclusions: The presented algorithm is user independent and provides highly accurate results for the orientation of the segmented electrodes for all angular constellations that typically occur in clinical cases., (© 2018 S. Karger AG, Basel.)

The inability to visualize airway smooth muscle (ASM) cells in vivo is a major obstacle in understanding their role in normal physiology and diseases. At present, there is no imaging modality available to assess ASM in vivo. Confocal endomicroscopy lacks the penetration depth and field of view, and conventional optical coherence tomography (OCT) does not have sufficient contrast to differentiate ASM from surrounding tissues. We have developed a birefringence microscopy platform that leverages the micro-organization of tissue to add further dimension to traditional OCT. We have used this technology to validate ASM measurements in ex vivo swine and canine studies, visualize and characterize volumetric representations of ASM in vivo, and quantify and predict ASM contractile force as a function of optical retardation. We provide in vivo images and volumetric assessments of ASM in living humans and document structural disease variations in subjects with mild asthma. The opportunity to link inflammatory responses to ASM responses and to link ASM responses to clinical responses and outcomes could lead to an increased understanding of diseases of the airway and, ultimately, to improved patient outcomes., (Copyright © 2016, American Association for the Advancement of Science.)

To improve (pre)malignant lesion identification in Barrett's esophagus (BE), recent research focuses on new developments in fluorescence imaging and spectroscopy to enhance tissue contrast. Our aim was to validate the chorioallantoic membrane (CAM) model as a preclinical tool to study the fluorescence characteristics such as autofluorescence and exogenously induced fluorescence of human Barrett's tissue. Therefore, esophageal biopsy specimens from Barrett's patients were freshly grafted onto the CAM of fertilized hen's eggs to simulate the in vivo situation. The BE biopsy specimens stayed between 1 and 9 days on the CAM to study the persistence of vitality. Fluorescence spectroscopy was performed using six excitation wavelengths (369, 395, 400, 405, 410, 416 nm). Obtained autofluorescence spectra were compared with in vivo spectra of an earlier study. Exogenous administration of 5-aminolevulinic-acid to the biopsy specimens was followed by fluorescence spectroscopy at several time points. Afterwards, the biopsy specimens were harvested and histologically evaluated. In total, 128 biopsy specimens obtained from 34 patients were grafted on the CAM. Biopsy specimens which stayed on average 1.7 days on the CAM were still vital. Autofluorescence spectra of the specimens correlated well with in vivo spectra. Administered 5-aminolevulinic-acid to the biopsy specimens showed conversion into protoporphyrin-IX. In conclusion, we showed that grafting freshly collected human BE biopsy specimens on the CAM is feasible. Our results suggest that the CAM model might be used to study the fluorescence behavior of human tissue specimens. Therefore, the CAM model might be a preclinical research tool for new photosensitizers.

Endoscopic surveillance is recommended for patients with Barrett's esophagus (BE) to detect high-grade intraepithelial neoplasia (HGIN) or early cancer (EC). Early neoplasia is difficult to detect with white light endoscopy and random biopsies are associated with sampling error. Fluorescence spectroscopy has been studied to distinguish non-dysplastic Barrett's epithelium (NDBE) from early neoplasia. The Optical Biopsy System (OBS) uses an optical fiber integrated in a regular biopsy forceps. This allows real-time spectroscopy and ensures spot-on correlation between the spectral signature and corresponding physical biopsy. The OBS may provide an easy-to-use endoscopic tool during BE surveillance. We aimed to develop a tissue-differentiating algorithm and correlate the discriminating properties of the OBS with the constructed algorithm to the endoscopist's assessment of the Barrett's esophagus. In BE patients undergoing endoscopy, areas suspicious for neoplasia and endoscopically non-suspicious areas were investigated with the OBS, followed by a correlating physical biopsy with the optical biopsy forceps. Spectra were correlated to histology and an algorithm was constructed to discriminate between HGIN/EC and NDBE using smoothed linear dicriminant analysis. The constructed classifier was internally cross-validated and correlated to the endoscopist's assessment of the BE segment. A total of 47 patients were included (39 males, age 66 years): 35 BE patients were referred with early neoplasia and 12 patients with NDBE. A total of 245 areas were investigated with following histology: 43 HGIN/EC, 66 low-grade intraepithelial neoplasia, 108 NDBE, 28 gastric or squamous mucosa. Areas with low-grade intraepithelial neoplasia and gastric/squamous mucosa were excluded. The area under the receiver operating characteristic curve of the constructed classifier was 0.78. Sensitivity and specificity for the discrimination between NDBE and HGIN/EC of OBS alone were 81% and 58% respectively. When OBS was combined with the endoscopist's assesssment, sensitivity was 91% and specificity 50%. If this protocol would have guided the decision to obtain biopsies, half of the biopsies would have been avoided, yet 4/43 areas containing HGIN/EC (9%) would have been inadvertently classified as unsuspicious. In this study, the OBS was used to construct an algorithm to discriminate neoplastic from non-neoplastic BE. Moreover, the feasibility of OBS with the constructed algorithm as an adjunctive tool to the endoscopist's assessment during endoscopic BE surveillance was demonstrated. These results should be validated in future studies. In addition, other probe-based spectroscopy techniques may be integrated in this optical biopsy forceps system., (© 2014 International Society for Diseases of the Esophagus.)

In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (∼500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb).

Early neoplasia arising from Barrett's esophagus is often small, focally distributed and endoscopically poorly visible, and random four-quandrant biopsies may easily miss early lesions. Advanced imaging techniques, such as (auto)fluorescence-based modalities, aim to increase the detection rate of early lesions or the yield of random biopsies. Fluorescence-based light-tissue interaction has been designed successfully in point-probe differentiating spectroscopy systems or integrated into wide-field endoscopic systems such as autofluorescence imaging (AFI). In this review, we discuss the most recent advances in fluorescence spectroscopy and imaging for detecting early Barrett's neoplasia. A spectroscopy probe, integrated into regular biopsy forceps, was shown to offer decent discriminatory capabilities, while ensuring spot-on correlation between the measured area and the corresponding histology. With this tool, surveillance endoscopy with random biopsies may become more efficient and sensitive. AFI was shown to increase the targeted detection of early neoplasia. However, random biopsies could compensate for this effect. The clinical impact of AFI on the diagnosis and the treatment of early neoplasia is limited, and yet AFI may offer a novel approach in biomarker-based risk-stratification models. Moreover, in combination with new, readily available contrast agents such as fluorescent lectins, fluorescence imaging may receive renewed interest.

Background & Aims: Studies have reported that autofluorescence imaging (AFI) increases targeted detection of high-grade intraepithelial neoplasia (HGIN) and intramucosal cancer (IMC) in patients with Barrett's esophagus (BE). We analyzed data from trials to assess the clinical relevance of AFI-detected lesions., Methods: We collected information on 371 patients with BE, along with endoscopy and histology findings, from databases of 5 prospective studies of AFI (mean age, 65 years; 305 male). We compared these data with outcomes of treatment and follow-up. Study end points included the diagnostic value of AFI (proportion of surveillance patients with HGIN or IMC detected only by AFI-targeted biopsies) and value of AFI in selection of therapy (the proportion of patients for which detection of an HGIN or IMC lesion by AFI changed the treatment strategy based on white-light endoscopy or random biopsy analysis)., Results: Of study participants, 211 were referred for surveillance and 160 were referred for early stage neoplasia; HGIN or IMC were diagnosed in 147 patients. In 211 patients undergoing surveillance, 39 had HGIN or IMC (23 detected by white-light endoscopy, 11 detected by random biopsies, 5 detected by AFI). So, the diagnostic value of AFI was 5 (2%) of 211. In 24 patients, HGIN or IMC was diagnosed using only AFI. In 33 patients, AFI detected additional HGINs or IMCs next to lesions detected by primary white-light endoscopy. Lesions detected by AFI were treated in 57 patients: 26 patients underwent radiofrequency ablation and showed full remission of neoplasia, whereas 31 underwent endoscopic resection and 6 were found to have IMC. The value of AFI in selection of therapy was 6 (2%) of 371., Conclusions: Based on an analysis of data from clinical trials of patients with BE, detection of lesions by AFI has little effect on the diagnosis of early stage neoplasia or therapeutic decision making. AFI therefore has a limited role in routine surveillance or management of patients with BE., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In Barrett's esophagus (BE), second-generation autofluorescence imaging (AFI-II) improves targeted detection of high-grade intra-epithelial neoplasia (HGIN) and early cancer (EC), yet suffers from high false-positive (FP) rates. The newest generation AFI (AFI-III) specifically targets fluorescence in malignant cells and may therefore improve detection of early neoplasia and reduce FP rate. The aim was to compare AFI-III with AFI-II for endoscopic detection of early neoplasia in BE. BE patients with endoscopically inconspicuous neoplasia underwent two diagnostic endoscopies (AFI-II/AFI-III) in a single session. End-points: number of patients and lesions with HGIN/EC detected with AFI-II and AFI-III after white-light endoscopy (WLE) and the value of reinspection of AFI-positive areas with WLE and narrow-band imaging. Forty-five patients were included (38 males, age 65 years). Nineteen patients showed HGIN/EC. AFI-II inspection after WLE increased detection of HGIN/EC from 9 to 15 patients (47 to 79%); AFI-III increased detection from 9 to 17 patients (47 to 89%). WLE plus random biopsies diagnosed 13/19 (68%) HGIN/EC patients. One hundred and four abnormal AFI areas were inspected; 23 (22%) showed HGIN/EC. AFI-II increased detection of HGIN/EC from 10 to 18 lesions (43 to 78%). AFI-III increased detection from 10 to 20 lesions (43-87%). FP rate was 86% for AFI-II and AFI-III. Reinspection with WLE or narrow-band imaging reduced FP rate to 21% and 22%, respectively, but misclassified HGIN/EC lesions as unsuspicious in 54% and 31%, respectively. This first feasibility study on third-generation AFI again showed improved targeted detection of HGIN/EC in BE. However, the results do not suggest AFI-III performs significantly better than conventional AFI-II., (© 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Objective: Fluorescence spectroscopy has the potential to detect early cellular changes in Barrett's oesophagus before these become visible. As the technique is based on varying concentrations of intrinsic fluorophores, each with its own optimal excitation wavelength, it is important to assess the optimal excitation wavelength(s) for identification of premalignant lesions in patients with Barrett's oesophagus., Methods: The endoscopic spectroscopy system used contained five (ultra)violet light sources (λexc=369-416 nm) to generate autofluorescence during routine endoscopic surveillance. Autofluorescence spectroscopy was followed by a biopsy for histological assessment and spectra correlation. Three intensity ratios (r1, r2, r3) were calculated by dividing the area, A, under the spectral curve of selected emission wavelength ranges for each spectrum generated by each excitation wavelength λexc as follows (Equation is included in full-text article.). Double intensity ratios were calculated using two excitation wavelengths., Results: Fifty-eight tissue areas from 22 patients were used for autofluorescence spectra analysis. Excitation with 395, 405 or 410 nm showed a significant (P≤0.0006) differentiation between intestinal metaplasia and grouped high-grade dysplasia/early carcinoma for intensity ratios r2 and r3. A sensitivity of 80.0% and specificity of 89.5% with an area under the ROC curve of 0.85 was achieved using 395 nm excitation and intensity ratio r3., Conclusion: Double excitation showed no additional value over single excitation. The combination of 395 nm excitation and intensity ratio r3 showed optimal conditions to discriminate nondysplastic from early neoplasia in Barrett's oesophagus.

The polarization characteristics of birefringent tissues could be only partially obtained using linearly polarized light in polarization sensitive optical imaging. Here we analyze the change in polarization of backscattered light from birefringent structures versus the orientations of the incident polarizations using linearly, circularly and radially polarized light in a cross-polarized confocal microscope. A spatially variable retardation plate composed of eight sectors of λ/2 wave plates was used to transform linearly polarized light into a radially polarized light. Based on the experimental data obtained from ex-vivo measurements on human scalp hairs and in-vivo measurements on hair and skin, we exemplify that the underestimation of the birefringence content resulting from the orientation related effects associated with the use of linearly polarized light for imaging tissues containing wavy birefringent structures could be minimized by using radially polarized light.