Changing perspectives using nuclear brain imaging: clinical and methodological studies

In this thesis, clinical and methodological studies have been performed to add to the clarification of as yet insufficiently characterized neurobiological mechanisms in common neurologic and psychiatric conditions, including traumatic brain injury and its sequelae and compulsive pornography use. Using positron emission tomography (PET), we studied whether neuroinflammation was present in currently active kickboxers as a consequence of chronic repetetive head injury. The results show that this may be present in a subset of kickboxers, although no relation with the performance on neuropsychological tasks could be demonstrated. Future studies may elucidate whether this process could lead to symptoms later on, such as the development of chronic traumatic encephalopathy.Another clinical study focused on subjects with problematic pornography use. In contrast to what is commonly observed in substance use disorders, these subjects did not show typical dopaminergic D2/3 reductions in the striatum or hypofrontality. These findings suggest that the neurobiological mechanisms underlying addiction to complex psychological stimuli like pornography exposure may be fundamentally different from those underlying addiction to chemical substances.Finally, methodological studies were performed focusing on presynaptic dopaminergic imaging, which has a role in evaluating parkinsonism. Results indicate that slightly different patterns of presynaptic dopaminergic deficits may be present in different parkinsonian syndromes. This information may be used in the assessment of presynaptic dopaminergic scans in the clinic

Changing perspectives using nuclear brain imaging: clinical and methodological studies

In this thesis, clinical and methodological studies have been performed to add to the clarification of as yet insufficiently characterized neurobiological mechanisms in common neurologic and psychiatric conditions, including traumatic brain injury and its sequelae and compulsive pornography use. Using positron emission tomography (PET), we studied whether neuroinflammation was present in currently active kickboxers as a consequence of chronic repetetive head injury. The results show that this may be present in a subset of kickboxers, although no relation with the performance on neuropsychological tasks could be demonstrated. Future studies may elucidate whether this process could lead to symptoms later on, such as the development of chronic traumatic encephalopathy.Another clinical study focused on subjects with problematic pornography use. In contrast to what is commonly observed in substance use disorders, these subjects did not show typical dopaminergic D2/3 reductions in the striatum or hypofrontality. These findings suggest that the neurobiological mechanisms underlying addiction to complex psychological stimuli like pornography exposure may be fundamentally different from those underlying addiction to chemical substances.Finally, methodological studies were performed focusing on presynaptic dopaminergic imaging, which has a role in evaluating parkinsonism. Results indicate that slightly different patterns of presynaptic dopaminergic deficits may be present in different parkinsonian syndromes. This information may be used in the assessment of presynaptic dopaminergic scans in the clinic

Image Quality and Activity Optimization in Oncologic F-18-FDG PET Using the Digital Biograph Vision PET/CT System

The first Biograph Vision PET/CT system (Siemens Healthineers) was installed at the University Medical Center Groningen. Improved performance of this system could allow for a reduction in activity administration or scan duration. This study evaluated the effects of reduced scan duration in oncologic 18F-FDG PET imaging on quantitative and subjective imaging parameters and its influence on clinical image interpretation. Methods: Patients referred for a clinical PET/CT scan were enrolled in this study, received a weight-based 18F-FDG injected activity, and underwent list-mode PET acquisition at 180 s per bed position (s/bp). Acquired PET data were reconstructed using the vendor-recommended clinical reconstruction protocol (hereafter referred to as "clinical"), using the clinical protocol with additional 2-mm gaussian filtering (hereafter referred to as "clinical+G2"), and-in conformance with European Association of Nuclear Medicine Research Ltd. (EARL) specifications-using different scan durations per bed position (180, 120, 60, 30, and 10 s). Reconstructed images were quantitatively assessed for comparison of SUVs and noise. In addition, clinically reconstructed images were qualitatively evaluated by 3 nuclear medicine physicians. Results: In total, 30 oncologic patients (22 men, 8 women; age: 48-88 y [range], 67 ± 9.6 y [mean ± SD]) received a single weight-based (3 MBq/kg) 18F-FDG injected activity (weight: 45-123 kg [range], 81 ± 15 kg [mean ± SD]; activity: 135-380 MBq [range], 241 ± 47.3 MBq [mean ± SD]). Significant differences in lesion SUVmax were found between the 180-s/bp images and the 30- and 10-s/bp images reconstructed using the clinical protocols, whereas no differences were found in lesion SUVpeak EARL-compliant images did not show differences in lesion SUVmax or SUVpeak between scan durations. Quantitative parameters showed minimal deviation (∼5%) in the 60-s/bp images. Therefore, further subjective image quality assessment was conducted using the 60-s/bp images. Qualitative assessment revealed the influence of personal preference on physicians' willingness to adopt the 60-s/bp images in clinical practice. Although quantitative PET parameters differed minimally, an increase in noise was observed. Conclusion: With the Biograph Vision PET/CT system for oncologic 18F-FDG imaging, scan duration or activity administration could be reduced by a factor of 3 or more with the use of the clinical+G2 or the EARL-compliant reconstruction protocol

Skeletal ¹⁸F-PSMA-1007 uptake in prostate cancer patients

Background/objectives: Accurate and uniform interpretation and reporting of metastatic prostate cancer (PCa) lesions on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are indispensable. 18F-PSMA-1007 is increasingly used because of its favorable imaging characteristics. However, increased non-specific skeletal uptake may be an important pitfall of this radioligand. Therefore, we aimed to assess the interobserver variation in reporting skeletal 18F-PSMA-1007 uptake on PET/CT.Design/methods: In total, 33 18F-PSMA-1007 PET/CT scans of 21 patients with primary PCa and 12 patients with biochemical recurrence were included, and a total of 85 skeletal lesions were evaluated by three independent observers. The primary endpoint was the interobserver variability of the likelihood of malignancy of the skeletal lesions on both patient and lesion level (kappa analysis).Results: Observers qualified most lesions as not malignant (81–91%) and the overall mean interobserver agreement was moderate on both patient (κ: 0.54) and lesion level (κ: 0.55). In 52 lesions without corresponding CT substrate, the rating resulted in not malignant in 95–100%. Availability of additional imaging (60% of lesions) did not improve interobserver agreement (κ: 0.39 on lesion level) and resulted in unchanged rating for all observers in 78%.Conclusion: This interobserver analysis of skeletal 18F-PSMA-1007 uptake resulted in moderate agreement, in line with rates reported in literature. Importantly, the presence of non-specific skeletal uptake without CT substrate, as a potential shortcoming of 18F-PSMA-1007, did not impair interobserver agreement.</p

Image Quality and Semiquantitative Measurements on the Biograph Vision PET/CT System:Initial Experiences and Comparison with the Biograph mCT

In May 2018, the Biograph Vision PET/CT system was installed at the University Medical Center Groningen. This study evaluated the initial experiences with this new PET/CT system in terms of perceived image quality and semiquantitative analysis in comparison to the Biograph mCT as a reference. Methods: In total, 20 oncologic patients were enrolled and received a single 3 MBq/kg injected dose of 18F-FDG followed by a dual-imaging PET scan. Ten patients were scanned on the Biograph mCT first, whereas the other 10 patients were scanned on the Biograph Vision first. The locally preferred clinically reconstructed images were blindly reviewed by 3 nuclear medicine physicians and scored (using a Likert scale of 1–5) on tumor lesion demarcation, overall image quality, and image noise. In addition, these clinically reconstructed images were used for semiquantitative analysis by measurement of SUVs in tumor lesions. Images acquired using reconstructions conform with the European Association of Nuclear Medicine Research Ltd. (EARL) specifications were also used for measurements of SUV in tumor lesions and healthy tissues for comparison between systems. Results: The 18F-FDG dose received by the 14 men and 6 women (age range, 36–84; mean ± SD, 61 ± 16 y) ranged from 145 to 405 MBq (mean ± SD, 268 ± 59.3). Images acquired on the Biograph Vision were scored significantly higher on tumor lesion demarcation, overall image quality, and image noise than images acquired on the Biograph mCT (P < 0.001). The overall interreader agreement showed a Fleiss κ of 0.61 (95% confidence interval, 0.53–0.70). Furthermore, the SUVs in tumor lesions and healthy tissues agreed well (within 95%) between PET/CT systems, particularly when EARL-compliant reconstructions were used on both systems. Conclusion: In this initial study, the Biograph Vision showed improved image quality compared with the Biograph mCT in terms of lesion demarcation, overall image quality, and visually assessed signal-to-noise ratio. The 2 systems are comparable in semiquantitatively assessed image biomarkers in both healthy tissues and tumor lesions. Improved quantitative performance may, however, be feasible using the clinically optimized reconstruction settings

Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type glioblastoma

PURPOSE: (11)C-Methionine ((11)C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for survival correlation in patients with IDH wild type glioblastomas. METHODS: Thirteen IDH wild type glioblastoma patients underwent preoperative (11)C-MET PET. Both SUV-based parameters and volume-based parameters were calculated for each lesion. Kaplan-Meier curves with log-rank testing and Cox regression analysis were used for correlation between PET parameters and overall survival. RESULTS: Median overall survival for the entire cohort was 393 days. MTV (HR 1.136, p = 0.007) and TLMM (HR 1.022, p = 0.030) were inversely correlated with overall survival. SUV-based (11)C-MET PET parameters did not show a correlation with survival. In a paired analysis with other clinical parameters including age and radiotherapy dose, MTV and TLMM were found to be independent factors. CONCLUSIONS: MTV and TLMM, and not SUV, significantly correlate with overall survival in patients with IDH wild type glioblastomas. The incorporation of volume-based (11)C-MET PET parameters may lead to a better outcome prediction for this heterogeneous patient population

Diagnostic accuracy of positron emission tomography tracers for the differentiation of tumor progression from treatment-related changes in high-grade glioma:a systematic review and meta-analysis

Background: Post-treatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent response assessment in neuro-oncology (RANO) recommendations PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and meta-analysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: Pubmed, Web of Science and Embase were searched systematically. Study selection, data extraction and quality assessment were performed independently by two authors. Meta-analysis was performed using a bivariate random effects model when ≥ 5 studies were included. Results: 39 studies (11 tracers) were included in the systematic review. 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95%CI 72-92) and 84% (69-93), respectively. 18F-FET (7 studies, 172 lesions) demonstrated a sensitivity of 90% (81-95) and specificity of 85% (71-93). 11C-MET (8 studies, 151 lesions) sensitivity was 93% (80-98) and specificity was 82% (68-91). The number of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93-100% and 0-100% for 18F-FLT, 85-100% and 72-100% for 18F-FDOPA and 100% and 70-88% for 11C-CHO, respectively. Conclusion:18F-FET and 11C-MET, both amino-acid tracers, showed a comparable higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited, thus 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas

Postural and gait symptoms in de novo Parkinson's disease patients correlate with cholinergic white matter pathology

Item does not contain fulltex

No evidence for decreased D2/3 receptor availability and frontal hypoperfusion in subjects with compulsive pornography use

Pornographic addiction refers to an addiction model associated with compulsive and repeated use of pornographic material. Whether the use of pornography may indeed become addictive remains a matter of debate. The current study investigated whether compulsive pornography use (CPU) is accompanied by reduced D2/3 receptor availability in the striatum and frontal hypofunctionality. Male subjects between 18 and 50 years of age with and without CPU were recruited using online and newspaper advertisements. Questionnaires were used to the assess the severity of compulsive pornography use (CIUS) and symptoms of depression, impulsivity and sensation seeking. Dopaminergic imaging was performed using [11C]-raclopride PET. Striatal binding potentials (BPND) and regional frontal cerebral influx values (R1) of [11C]-raclopride were calculated. Arterial Spin Labeling (ASL) MRI was performed to assess regional cerebral blood flow. No group differences between striatal BPND's of [11C]-raclopride in subjects with (n = 15) and without (n = 10) CPU were detected. In CPU subjects, no correlation was found between the CIUS score and striatal BPND's. Cerebral R1 values in frontal brain regions and cerebral blood flow measurements did not differ between groups. The current study fails to provide imaging support for sharing similar neurobiological alterations as previously has been reported in other addictive modalities

Rapid Eye Movement Sleep Behavior Disorder:Abnormal Cardiac Image and Progressive Abnormal Metabolic Brain Pattern

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) is prodromal for α-synucleinopathies. OBJECTIVE: The aim of this study was to determine whether pathological cardiac [123 I]meta-iodobenzylguanidine scintigraphy ([123 I]MIBG) is associated with progression of [18 F]fluorodeoxyglucose-positron emission tomography-based Parkinson's disease (PD)-related brain pattern (PDRP) expression in iRBD. METHODS: Seventeen subjects with iRBD underwent [18 F]fluorodeoxyglucose-positron emission tomography brain imaging twice ~3.6 years apart. In addition, [123 I]MIBG and [123 I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computed tomography ([123 I]FP-CIT-SPECT) at baseline were performed. Olfactory, cognitive, and motor functions were tested annually. RESULTS: Twelve of 17 subjects had pathological [123 I]MIBG. At baseline, 6 of 12 of these expressed the PDRP (suprathreshold PDRP z score). At follow-up, 12 of 17 subjects had suprathreshold PDRP z scores, associated with pathological [123 I]MIBG in 92% and with pathological [123 I]FP-CIT-SPECT in 75%. Subjects with pathological [123 I]MIBG had higher PDRP z score change per year (P = 0.027). Three subjects phenoconverted to PD; all had pathological [123 I]MIBG and [123 I]FP-CIT-SPECT, suprathreshold baseline PDRP z scores, and hyposmia. CONCLUSIONS: Pathological [123 I]MIBG was associated with progressive and suprathreshold PDRP z scores at follow-up. Abnormal [123 I]MIBG likely identifies iRBD as prodromal PD earlier than pathological [123 I]FP-CIT-SPECT. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society