Quantitative nuclear cardiology using SPECT : evaluation of perfusion, function and innervation

The application of nuclear imaging for non-invasive assessment of cardiovascular diseases is well established. Although the visual assessment of myocardial perfusion will remain the mainstay for some time, the field is changing. Advancements in device technology, processing techniques and radiopharmaceuticals have shifted the field beyond the assessment of perfusion alone towards an integrated evaluation of perfusion, function and innervation. Quantitative nuclear cardiology is becoming ever more important in a clinical setting. And, while the improvements in automated quantification have increased the diagnostic accuracy, there are various factors that may induce inaccuracies. The dependence of functional MPS indices on, for example, the software package or the injection-acquisition time interval, are indistinct. Also the meaning of recently introduced functional parameters and their relation to other indices remain unclear. For innervation imaging, the lack of standardization regarding acquisition and processing still affect the clinical applicability of this technology. All these ambiguities of SPECT-based quantification are addressed in this thesis.VANDERWILT techniques, GE Healthcare, Invia Medical Imaging Solutions and Dutch Heart FoundationUBL - phd migration 201

Quantitative nuclear cardiology using SPECT : evaluation of perfusion, function and innervation

The application of nuclear imaging for non-invasive assessment of cardiovascular diseases is well established. Although the visual assessment of myocardial perfusion will remain the mainstay for some time, the field is changing. Advancements in device technology, processing techniques and radiopharmaceuticals have shifted the field beyond the assessment of perfusion alone towards an integrated evaluation of perfusion, function and innervation. Quantitative nuclear cardiology is becoming ever more important in a clinical setting. And, while the improvements in automated quantification have increased the diagnostic accuracy, there are various factors that may induce inaccuracies. The dependence of functional MPS indices on, for example, the software package or the injection-acquisition time interval, are indistinct. Also the meaning of recently introduced functional parameters and their relation to other indices remain unclear. For innervation imaging, the lack of standardization regarding acquisition and processing still affect the clinical applicability of this technology. All these ambiguities of SPECT-based quantification are addressed in this thesis

Comparison between a count-based and geometric-based approach for the assessment of left ventricular dyssynchrony: a gated SPECT myocardial perfusion scintigraphy study

Cardiovascular Aspects of Radiolog

Performance evaluation of Cerenkov luminescence imaging: a comparison of 68Ga with 18F

Background: Cerenkov Luminescence Imaging (CLI) is an emerging technology for intraoperative margin assessment. Previous research only evaluated radionuclide 18-Fluorine (18F); however, for future applications in prostate cancer, 68-Gallium (68Ga) seems more suitable, given its higher positron energy. Theoretical calculations predict that 68Ga should offer a higher signal-to-noise ratio than 18F; this is the first experimental confirmation. The aim of this study is to investigate the technical performance of CLI by comparing 68Ga to 18F. Results: The linearity of the system, detection limit, spatial resolution, and uniformity were determined with the LightPath imaging system. All experiments were conducted with clinically relevant activity levels in vitro, using dedicated phantoms. For both radionuclides, a linear relationship between the activity concentration and detected light yield was observed (R2 = 0.99). 68Ga showed approximately 22 times more detectable Cerenkov signal compared to 18F. The detectable activity concentration after a 120 s exposure time and 2 × 2 binning of 18F was 23.7 kBq/mL and 1.2 kBq/mL for 68Ga. The spatial resolution was 1.31 mm for 18F and 1.40 mm for 68Ga. The coefficient of variance of the uniformity phantom was 0.07 for the central field of view. Conclusion: 68Ga was superior over 18F in terms of light yield and minimal detection limit. However, as could be expected, the resolution was 0.1 mm less for 68Ga. Given the clinical constraints of an acquisition time less than 120 s and a spatial resolution < 2 mm, CLI for intraoperative margin assessment using 68Ga could be feasible

Comparison between a count-based and geometrical approach for the assessment of left ventricular dyssynchrony using myocardial perfusion scintigraphy

Cardiovascular Aspects of Radiolog

Haematotoxicity during peptide receptor radionuclide therapy: Baseline parameters differences and effect on patient's therapy course

BACKGROUND: Mainly severe (CTCAE grade 3-4) haematotoxicity during peptide receptor radionuclide therapy (PRRT) is reported in literature due to major clinical impact, however moderate (CTCAE grade 2) haematotoxicity is common and could affect therapy management. The aim of this study was to evaluate the haematotoxicity course during PRRT and to compare baseline parameters between haematotoxicity grades. METHODS: In this retrospective study, 100 patients with a neuroendocrine tumour treated with PRRT were included. Patients were treated with an aimed number of four cycles with 7.4 GBq [177Lu]Lu-DOTA-TATE administered every 10 weeks. Haematological assessment was performed at baseline and frequently up to 10 weeks after the fourth cycle. The lowest haematological value was graded according to CTCAE v5.0, and patients were classified using the highest observed grade. Differences in baseline parameters, including [68Ga]Ga-DOTA-TATE positive tumour volume, were evaluated between CTCAE grades. RESULTS: Four cycles were completed by 86/100 of patients, 4/100 patients discontinued due to haematotoxicity, and 10/100 patients due to progressive disease. The treatment course was adjusted due to haematotoxicity in 24/100 patients, including postponed next cycle (n = 17), reduced administered activity (n = 13), and both adjustments (n = 10). The most observed haematotoxicity grade was grade 0-1 in 54/100 patients, grade 2 in 38/100 and grade 3-4 in 8/100. Significant differences in baseline leucocyte, neutrophil and platelet counts were observed between grade 0-1 and grade 2. However, the correlation between baseline and lowest observed values was poor to moderate. No differences between haematotoxicity grades and baseline parameters or somatostatin receptor positive tumour volume was observed. CONCLUSIONS: The incidence of severe haematotoxicity was low with extensive screening and monitoring. The vast majority of patients (96/100) was not restricted in treatment continuation by haematotoxicity; therefore, our selection criteria appeared appropriate for safe PRRT treatment. Baseline parameters showed limited correlation with the degree of decline in haematological values

PD-L1 PET/CT Imaging with Radiolabeled Durvalumab in Patients with Advanced-Stage Non-Small Cell Lung Cancer

Better biomarkers are needed to predict treatment outcome in non-small cell lung cancer (NSCLC) patients treated with anti-programmed death1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors. PD-L1 immunohistochemistry has limited predictive value, possibly because of tumor heterogeneity of PD-L1 expression. Noninvasive PD-L1 imaging using Zr-89-durvalumab might better reflect tumor PD-L1 expression. Methods: NSCLC patients eligible for second-line immunotherapy were enrolled. Patients received 2 injections of Zr-89-durvalumab: one without a preceding dose of unlabeled durvalumab (tracer dose only) and one with a preceding dose of 750 mg of durvalumab, directly before tracer injection. Up to 4 PET/CT scans were obtained after tracer injection. After imaging acquisition, patients were treated with 750 mg of durvalumab every 2 wk. Tracer biodistribution and tumor uptake were visually assessed and quantified as SUV, and both imaging acquisitions were compared. Tumor tracer uptake was correlated with PD-L1 expression and clinical outcome, defined as response to durvalumab treatment. Results: Thirteen patients were included, and 10 completed all scheduled PET scans. No tracer-related adverse events were observed, and all patients started durvalumab treatment. Biodistribution analysis showed Zr-89-durvalumab accumulation in the blood pool, liver, and spleen. Serial imaging showed that image acquisition 120 h after injection delivered the best tumor-to-blood pool ratio. Most tumor lesions were visualized with the tracer dose only versus the coinjection imaging acquisition (25% vs. 13.5% of all lesions). Uptake heterogeneity was observed within (SUVpeak range, 0.2-15.1) and between patients. Tumor uptake was higher in patients with treatment response or stable disease than in patients with disease progression according to RECIST 1.1. However, this difference was not statistically significant (median SUVpeak , 4.9 vs. 2.4; P = 0.06). SUVpeak correlated better with the combined tumor and immune cell PD-L1 score than with PD-L1 expression on tumor cells, although neither was statistically significant (P = 0.06 and P = 0.93, respectively). Conclusion: Zr-89-durvalumab was safe, without any tracer-related adverse events, and more tumor lesions were visualized using the tracer dose-only imaging acquisition. Zr-89-durvalumab tumor uptake was higher in patients with a response to durvalumab treatment but did not correlate with tumor PD-L1 immunohistochemistry.Pathogenesis and treatment of chronic pulmonary disease

International recommendations for personalised selective internal radiation therapy of primary and metastatic liver diseases with yttrium-90 resin microspheres.

A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 ( &lt;sup&gt;90&lt;/sup&gt; Y)-resin microspheres. A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with &lt;sup&gt;90&lt;/sup&gt; Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and &lt;sup&gt;99m&lt;/sup&gt; Tc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the &lt;sup&gt;90&lt;/sup&gt; Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with &lt;sup&gt;90&lt;/sup&gt; Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). Practitioners are encouraged to work towards adoption of these recommendations

Propensity score-matched analysis of oncological outcome between stent as bridge to surgery and emergency resection in patients with malignant left-sided colonic obstruction

Background: Although self-expandable metal stent (SEMS) placement as bridge to surgery (BTS) in patients with left-sided obstructing colonic cancer has shown promising short-term results, it is used infrequently owing to uncertainty about its oncological safety. This population study compared long-term oncological outcomes between emergency resection and SEMS placement as BTS.Methods: Through a national collaborative research project, long-term outcome data were collected for all patients who underwent resection for left-sided obstructing colonic cancer between 2009 and 2016 in 75 Dutch hospitals. Patients were identified from the Dutch Colorectal Audit database. SEMS as BTS was compared with emergency resection in the curative setting after 1: 2 propensity score matching.Results: Some 222 patients who had a stent placed were matched to 444 who underwent emergency resection. The overall SEMS-related perforation rate was 7.7 per cent (17 of 222). Three-year locoregional recurrence rates after SEMS insertion and emergency resection were 11-4 and 13.6 per cent (P= 0-457), disease-free survival rates were 58-8 and 52.6 per cent (P= 0-175), and overall survival rates were 74-0 and 68-3 per cent (P= 0.231), respectively. SEMS placement resulted in significantly fewer permanent stomas (23.9 versus 45.3 per cent; P < 0-001), especially in elderly patients (29.0 versus 57.9 per cent; P < 0-001). For patients in the SEMS group with or without perforation, 3-year locoregional recurrence rates were 18 and 11.0 per cent (P= 0.432), disease-free survival rates were 49 and 59.6 per cent (P= 0-717), and overall survival rates 61 and 75.1 per cent (P= 0.529), respectively.Conclusion: Overall, SEMS as BTS seems an oncologically safe alternative to emergency resection with fewer permanent stomas. Nevertheless, the risk of SEMS-related perforation, as well as permanent stoma, might influence shared decision-making for individual patients.Research into fetal development and medicin