Dosimetric implications of kidney anatomical volume changes in 177Lu-DOTATATE therapy.

INTRODUCTION: This study aims to evaluate the use of CT-based whole kidney parenchyma (WKP) segmentation in 177Lu-DOTATATE dosimetry. Specifically, it investigates whether WKP volumes change during treatment and evaluates the accuracy of applying a single delineated WKP volume for dosimetry. Furthermore, it aims to determine the cause of WKP volume changes-whether caused by radiation or amino acid infusion-by comparing them with spleen volume changes as a marker for radiation-induced alterations. METHODS: SPECT/CT images of 18 patients were acquired over the abdomen approximately 4 h (h) (D0), 24 h (D1), 48 h (D2) and 168 h (D7) post-administration of 177Lu-DOTATATE. CT guided WKP volumes were measured before (baseline) and during treatment. Kidney activity concentrations at each time point were derived from CT-segmented WKP overlaid on SPECT scans. The accuracy of using WKP segmentation from a single CT for all time points was assessed against the gold standard of segmenting each WKP individually. Time-integrated activity calculations were based on a tri-exponential curve fit of the kidney activity concentration over time. Kidney absorbed doses were estimated under the assumption of local energy deposition. Additionally, the impact of various partial volume correction methods on dosimetry was evaluated. RESULTS: Whole-kidney parenchyma (WKP) volumes, ranging from 31 to 243 mL, showed a gradual increase from baseline (mean ± SD = 130.6 ± 46.1 mL) at the initial time points D0 (138.5 ± 44.7 mL) and D1 (139.4 ± 41.6 mL), followed by a slight decrease at D2 (132.8 ± 44.5 mL) and a further decrease at D7 (129.2 ± 42.7 mL). The volume increase at D0 and D1 was statistically significant. Spleen volume did not change during treatment, suggesting that amino acid infusion rather than irradiation effects caused WKP volume changes. Bland-Altman analysis revealed WKP volume biases of 8.77% (D0 vs. BL), 10.77% (D1 vs. BL), 1.10% (D2 vs. BL), and 1.10% (D7 vs. BL), with corresponding uncertainties of 24.4%, 23.6%, 25.4%, and 25.4%, respectively. When WKP segmentation from a single CT is applied across all SPECTs, these WKP volume changes could overestimate the activity concentration and mean absorbed doses up to 4.3% and 2.5%, respectively. The absorbed dose uncertainties using a recovery coefficient (RC) of 0.85 for single-time-point WKP delineation increase the absorbed dose uncertainty by 4% compared to the use of patient-specific RCs and time specific segmentation of WKP volumes. CONCLUSIONS: Kidney volume exhibited significant variation form D0 to D7, affecting the precision of dosimetry calculation, primarily due to errors in whole-kidney parenchyma (WKP) delineation. Notably, using WKP segmentation from a single CT scan applied to sequential SPECT images introduce further uncertainty and may lead to an overestimation of the absorbed dose. The fluctuations in kidney volume are most likely attributable to amino acid infusion.

Refining Cardiovascular Calcification in the Appraisal of Ischemic Heart.

BACKGROUND: Even in asymptomatic patients, there is a high association of ischemia on myocardial perfusion scans in those with coronary artery calcification or valvular calcifications. Patients without coronary artery calcifications have exceeding-low rates of cardiovascular events. The absence of cardiovascular calcification, including coronary artery, valvular, and thoracic aorta is a strong negative predictor of myocardial ischemia. In individuals with suspected ischemia who had chest computed tomography imaging, evaluation for cardiovascular calcification (coronary artery, valves, and thoracic aorta) is an invaluable tool to guide management for further diagnostic imaging. We hypothesize that the complete absence of cardiovascular calcification has a high negative predictive value for defects in myocardial perfusion imaging such as single-photon emission computed tomography (SPECT) or positron emission tomography (PET). METHODS: Non-contrast computed tomography performed for SPECT/PET CT attenuation correction from March 1, 2017, to September 30, 2017, were retrospectively reviewed for the absence of cardiovascular calcification by a cardiologist and radiologist who were blinded to patients' medical history. Medical records were reviewed to include patient demographics and medical history. A total of 132 patients were analyzed. RESULTS: Of the 132 patients without calcifications, seven patients had small myocardial perfusion defects suggestive of ischemia or infarct, but none were considered significant defects. Of these seven patients, six were managed medically and one was from an outside institution with no follow-up data. Two of the seven patients had follow-up invasive angiography or coronary CTA that did not show significant atherosclerotic coronary artery disease. CONCLUSION: A complete absence of cardiovascular calcification indicates a 100% negative predictive value for a significant perfusion defect on same-day confirmatory nuclear stress testing. Patients with suspected ischemia but absent cardiovascular calcifications can be safely managed medically without further testing for ischemia.

Cardiovascular imaging research and innovation in 2023.

In 2023, cardiovascular imaging has made significant advancements, in terms of technology, pathophysiology, and clinical application. In this review, the most recent research findings in the field of cardiovascular imaging are discussed. Artificial intelligence and large population cohorts, together with several technical improvements, have had a crucial impact on the technological advancements of echocardiography, cardiovascular magnetic resonance, computed tomography (CT), and nuclear medicine. In the field of ischaemic heart disease, it has been demonstrated that appropriate non-invasive imaging strategies improve patients' management and reduce invasive procedures and the need for additional testing at follow-up. Moreover, improvements in plaque characterization with CT are an expanding field of research with relevant implications for the prediction of disease severity, evolution, and response to treatment. In the field of valvular heart disease, imaging techniques have advanced alongside improvements in transcatheter treatment for aortic stenosis, mitral, and tricuspid regurgitation. Finally, in the field of heart failure and cardiomyopathies, cardiovascular imaging has reinforced its crucial role in early diagnosis and risk evaluation, showcasing advanced techniques that outperform traditional methods in predicting adverse outcomes.

Radionuclide Imaging of the Neuroanatomical and Neurochemical Substrate of Cognitive Decline in Parkinson's Disease.

Cognitive impairment is a frequent manifestation of Parkinson's disease (PD), resulting in decrease in patients' quality of life and increased societal and economic burden. However, cognitive decline in PD is highly heterogenous and the mechanisms are poorly understood. Radionuclide imaging techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT) have been used to investigate the neurochemical and neuroanatomical substrate of cognitive decline in PD. These techniques allow the assessment of different neurotransmitter systems, changes in brain glucose metabolism, proteinopathy, and neuroinflammation in vivo in PD patients. Here, we review current radionuclide imaging research on cognitive deficit in PD with a focus on predicting accelerating cognitive decline. This research could assist in the development of prognostic biomarkers for patient stratification and have utility in the development of ameliorative or disease-modifying therapies targeting cognitive deficit in PD.

Significant Association of Serum Albumin With the Severity of Coronary Microvascular Dysfunction Using Dynamic CZT-SPECT.

OBJECTIVE: Both low serum albumin (SA) concentration and coronary microvascular dysfunction (CMD) are risk factors for the development of heart failure (HF). We hypothesized that SA concentration is associated with myocardial flow reserve (MFR) and implicated in pathophysiological mechanism of HF. METHODS: We retrospectively studied 454 patients undergoing dynamic cardiac cadmium-zinc-telluride myocardial perfusion imaging from April 2018 to February 2020. The population was categorized into three groups according to SA level (g/dL): Group 1: >4, Group 2: 3.5-4, and Group 3: <3.5. Myocardial blood flow (MBF) and myocardial flow reserve (MFR, defined as stress/rest MBF ratio) were compared. RESULTS: The mean age of the whole cohort was 66.2 years, and 65.2% were men. As SA decreased, stress MBF (mL min-1 g-1) and MFR decreased (MBF: 3.29 ± 1.03, MFR: 3.46 ± 1.33 in Group 1, MBF: 2.95 ± 1.13, MFR: 2.51 ± 0.93 in Group 2, and MBF: 2.64 ± 1.16, MFR: 1.90 ± 0.50 in Group 3), whereas rest MBF (mL min-1 g-1) increased (MBF: 1.05 ± 0.42 in Group 1, 1.27 ± 0.56 in Group 2, and 1.41 ± 0.61 in Group 3). After adjusting for covariates, compared with Group 1, the odds ratios for impaired MFR (defined as MFR < 2.5) were 3.57 (95% CI: 2.32-5.48) for Group 2 and 34.9 (95% CI: 13.23-92.14) for Group 3. The results would be similar if only regional MFR were assessed. The risk prediction for CMD using SA was acceptable, with an AUC of 0.76. CONCLUSION: Low SA concentration was associated with the severity of CMD in both global and regional MFR as well as MBF.

[Validation of Quantitative Accuracy and Variability in 177Lu Imaging Using Monte Carlo Simulation].

PURPOSE: To predict side effects and optimize injection doses in the dosimetry of 177Lu imaging, highly accurate quantitative SPECT images are required. Monte Carlo simulations were performed to verify the accuracy and variability of quantitative values for 177Lu imaging under various imaging conditions. METHODS: SPECT data of NEMA body phantom were assumed to simulate intrahepatic tumors 6 h after administration of 7.4 GBq of 177Lu-Dotatate. SPECT data were acquired using the SIMIND program with different combinations of collimators and energy windows. For variability evaluation, 30 SPECT images with Poisson noise were generated for each acquisition time. The relative error was evaluated for accuracy evaluation, and the coefficient of variation was estimated for variability evaluation. RESULTS: The accuracy of BG quantification was less than 10% relative error. The accuracy of hot sphere quantification was highest with the combination of MEGP and an energy window of 208 keV±10%. However, the accuracy of hot sphere quantification decreased significantly with decreasing hot sphere diameter. Variability varied with imaging conditions and improved with longer acquisition time. CONCLUSION: Monte Carlo simulations revealed the accuracy and variability of quantitative values for each SPECT imaging condition for 177Lu imaging.

Going beyond summed stress scores: Correlating global and territorial coronary flow reserve by single photon emission tomography with routine myocardial perfusion imaging.

a Background: Technological advancement in the recent years has enabled the application of single photon emission tomography (SPECT) to evaluate myocardial blood flow (MBF). This method offers increased sensitivity in the assessment of coronary health, quantifiable through non-invasive imaging beyond the more conventional methods such as with myocardial perfusion imaging (MPI). b Aims: To correlate MBF, derived by dynamic SPECT, both global and by coronary territories to the summed stress scores (SSS) on conventional MPI. c Methods: Images obtained from dipyridamole-gated SPECT MPI stress and rest studies performed on recruited subjects were examined. We calculated the global and regional coronary flow reserve (CFR) via a standard software package, taken as the ratio of stress MBF to rest MBF, using CFR<2.5 as the cut off. d Results: Amongst the 90 recruited subjects (mean age 67 ± 8 years; of which 76% were males), 49% had MPI within normal limits (summed stress score (SSS) 0-3; Left ventricular ejection fraction (LVEF) > 50%). We observed a progressive reduction in global and regional CFR across the normal SSS category to that of severely abnormal (SSS >13). Reduced global CFR with correspondent lower CFR across the regional arteries were detected in scans within normal limits of MPI scans in subjects who were older (69 ± 7 vs. 62 ± 9 years, p = 0.034). Decreasing CFR was significantly associated with increasing age across the regional arteries. e Conclusion: In our study we depict the global and regional MBF values obtained via SPECT MPI in correlation to the respective SSS categories. Our data proposes that dynamic SPECT has a part in refining cardiac risk stratification, particularly in the older adult population, who are at greater risk.

Dosimetry during iodine-131 therapy - a technical point of view from a single centre's own experience.

BACKGROUND: Nuclear medicine uses radionuclides in medicine for diagnosis, staging, therapy, and monitoring the response to therapy. The application of radiopharmaceutical therapy for the treatment of certain diseases is well-established, and the field is expanding. Internal dosimetry is multifaceted and includes different workflows, as well as various calculations based on patient- specific dosimetry. AIM: The objective of this study was to introduce the technical issues which might occur during iodine-131 (¹³¹I) dosimetry performed in nuclear medicine departments. MATERIAL AND METHODS: Retrospective analysis was performed on a group of 44 patients with papillary thyroid cancer who between May 2021 and October 2021 underwent a 131I treatment: 80-100 mCi (2200-3700 MBq, based on the previous medical history and stage of the disease). Patients underwent a series of ¹³¹I therapy scans using gamma camera Discovery NM 670 CT. Whole body scan (WBS) was performed 2, 4, 24 and 48 hours after ¹³¹I administration. Additionally, after 24 hours of single photon emission computed tomography/ computed tomography, two fields of view (SPECT/CT 2-FOV) were performed from the mid-head to the bladder. RESULTS: During the dosimetry procedure, several issues arise. Firstly, after receiving therapeutic doses of ¹³¹I, patients should remain in their rooms until the appropriate activity is achieved before being transported to the diagnostic room. Secondly, the walls between examination rooms meet the requirements for accurate diagnosis but not for therapy, leading to the occurrence of artefacts in patients examined behind the wall, potentially influencing the examination results. Thirdly, personnel in the control room also experience additional exposure (10 times greater than in the case of standard diagnostic procedure). CONCLUSIONS: The dosimetry in patients in whom therapeutic procedures are performed with the use of isotopes is mandatory according to Polish and European law, technical issues which occur during the dosimetry procedures might influence the organization of the work in departments.

Cerebellar and Occipital Alterations in Brain Perfusion in a Patient With Post-acute COVID-19 Encephalopathy Misdiagnosed As Primary Psychotic Disorder.

We describe the case of an unvaccinated 21-year-old Japanese male who experienced psychotic symptoms attributed to encephalopathy, known as post-acute COVID-19 syndrome (PACS). One week after his discharge following the remission of a SARS-CoV-2 infection, he experienced hyperactive delirium and unexpected movements of his limbs. As COVID-19-associated encephalopathy was suspected as a cause of the psychotic symptoms, he was admitted to the Department of Neurology. He received antiviral and steroid pulse therapy, but his psychiatric symptoms did not improve completely. Consequently, he was admitted to our psychiatric ward with a diagnosis of a primary psychotic disorder. Although he did not take psychopharmacotherapy, he gradually achieved a remission of psychiatric symptoms. At three months post-SARS-CoV-2 infection, single-photon emission computed tomography (SPECT) revealed hypoperfusion in the bilateral cerebellar dentate nuclei and occipital lobes. However, no abnormal findings were observed on fluorine-18 fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) at six months after the infection. This case indicates that (1) brain perfusion SPECT can be effective for detecting functional alterations in post-acute COVID-19-associated encephalopathy, and (2) it is necessary to carefully monitor patients' progress instead of quickly diagnosing a primary psychotic disorder.

Utility of 99mTc-Sestamibi Single-Photon Emission Computed Tomography (SPECT)/CT Single Imaging Strategy in the Preoperative Localization of Parathyroid Adenoma.

Background Primary hyperparathyroidism is an endocrinopathy associated with dysregulated calcium homeostasis. The most common etiology is a parathyroid adenoma most definitely managed via a parathyroidectomy. The two main surgical approaches include a minimally invasive parathyroidectomy (MIP) and open four-gland exploration (4-GE). MIP is the preferred operative strategy since it is associated with less postoperative complications. Accurate preoperative imaging is essential in informing the optimal approach to surgery. MIP is only considered if adenoma is able to be localized precisely. The most commonly used imaging modality includes ultrasound and sestamibi single-photon emission computed tomography (SPECT)/CT, either as a single or combination strategy. Other options include MRI, PET, and 4D CT. There is no universally accepted preoperative imaging strategy. The literature is discordant and recommendations proposed by existing guidelines are incongruous. Objectives This study aimed to evaluate currently utilized preoperative parathyroid imaging modalities at our institution and correlate them with surgical and histological findings to determine the most efficient imaging strategy to detect adenomas for our patient cohort. This will ultimately guide the best surgical approach for patients receiving parathyroidectomies. Methods This is a retrospective observational study of all patients undergoing first-time surgery for biochemically proven primary hyperparathyroidism at our institution over the past five years. Multiple data points were collected including modality of preoperative disease localization, operation type, final histopathology, biochemical investigations, and cure rate. Patients were categorized into one of three groups based on the method of disease localization. Results A total of 244 patients had parathyroidectomies performed at our institution in the past five years from January 2018 to December 2022. Ninety-six percent (n=235) of all patients received dual imaging preoperatively with SPECT/CT and ultrasound performed on the same day and therefore included in this study. A total of 64.3% (n=151) underwent MIP. Eighty percent (n=188) of all histopathology revealed adenomas and 26.8% (n=63) of patients had adenoma localized on SPECT/CT only (sensitivity: 58.1%, specificity: 71%, and positive predictive value {PPV}: 85.7%). A total of 9.8% (n=23) had adenoma localized on ultrasound only (sensitivity: 15.6%, specificity: 73.3%, and PPV: 65.2%). A total of 45.1% (n=106) were dual localized on both SPECT/CT and ultrasound (sensitivity: 75.6%, specificity: 46.6%, and PPV: 84.9%). The cure rate was 91.5% in the dual-localized group, 86% in the dual-unlocalized group, and 96.5% when localized with SPECT/CT alone. Conclusion A dual-imaging modality with SPECT/CT and ultrasound should remain the first-line imaging strategy. This approach has higher sensitivity rates and poses no inherent patient or surgical-related risks. Patients with disease unlocalized on SPECT/CT alone had a positive predictive value, specificity, and likelihood ratio for adenoma detection comparable to dual-localized patients. Therefore, SPECT/CT alone is sufficient for directing MIP in the presence of a negative ultrasound.

Radiotracers for Imaging of Inflammatory Biomarkers TSPO and COX-2 in the Brain and in the Periphery.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, autoimmune diseases, pulmonary and cancer. Inflammation in the brain is marked by the upregulation of translocator protein (TSPO) in microglia. High TSPO levels are also found, for example, in macrophages in cases of rheumatoid arthritis and in malignant tumor cells compared to their relatively low physiological expression. The same applies for cyclooxgenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable the monitoring of the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers, not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases such as rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

Diagnosis and treatment of Watershed strokes: a narrative review.

Watershed strokes have been described previously as ischemic strokes located in vulnerable border zones between brain tissue supplied by the anterior, posterior, and middle cerebral arteries in the distal junction between two non-anastomotic arterial territories. Ischemic strokes in border zones are well-recognized entities and well-described in terms of imaging features, but the pathophysiological mechanism of brain injury production is not fully defined. Border zone ischemia is caused by cerebral hypoperfusion through decreased cerebral blood flow and arterial embolism in unstable atheroma plaque. It is often difficult to say which mechanisms are fully responsible for producing cerebral ischemic lesions. This review aimed to highlight the imaging aspect of watershed strokes and to correlate the clinical characteristics of this type of stroke with the diagnostic algorithm for optimal therapeutic management. Neurologists should promptly recognize this type of stroke and investigate its etiology in the shortest possible time.

Predictors of diastolic deceleration time of coronary flow velocity of infarct related and reference coronary artery assessed by transthoracic Doppler echocardiography in the chronic phase of successfully reperfused anterior myocardial infarction: relation to infarct size.

Introduction: High-frequency transthoracic Doppler echocardiography (TDE) enables the assessment of flow velocity and velocity pattern in different coronary arteries, including the assessment of diastolic deceleration time (DDT) of coronary flow velocity. Short DDT of infarct related artery (IRA) (<600 msec) in the acute phase of anterior myocardial infarction (MI) is the predictor of adverse left ventricular (LV) remodeling and prognosis. The significance of DDT of coronary flow velocity assessment in the chronic phase of anterior MI is not well established. Our study aimed to establish the predictors of DDT of the coronary flow velocity of infarct related (left anterior descendent-DDT of LAD) and reference coronary artery, evaluated by TDE, and to assess their relation to infarct size in the chronic phase of successfully reperfused first anterior MI. Methods: Our study included 40 consecutive patients (34 men, mean age 52 ± 12 years) one month after the first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of LV volumes, ejection fraction, and percentage of the myocardium with fixed perfusion abnormalities and echocardiographic examination including the evaluation of DDT of IRA and reference coronary artery TDE. Results: DDT of LAD correlated significantly to the WMSI (r = -0.467, p = 0.002), LV end-systolic volume (r = -0.412, p = 0.008), LV ejection fraction (r = 0.427, p = 0.006), while the strongest correlation was observed between DDT of LAD and the extent of fixed perfusion abnormality (r = -0.627, p < 0.0001), Multivariate analysis revealed percentage of fixed perfusion abnormalities along with DDT of reference coronary artery as the independent predictors of DDT of IRA. DDT of IRA shorter than 886 msec predicts large fixed perfusion abnormalities (>20%) with a sensitivity of 89% and specificity of 62% (AUC 0.842). Conclusion: DDT of LAD assessed by TDE in the chronic phase of successfully reperfused first anterior MI is a usefull variable for the assessment of microcirculatory function that exclusively reflects the extent of microvascular damage and relates to infarct size.

The new bone WB-SPECT/CT: hybrid, from head-to-toe and digital! Is it worth the effort?

INTRODUCTION: A bone scan (BS) plays a pivotal role in many oncological and non-oncological conditions. The planar BS is characterized by high sensitivity but low specificity. With respect to planar imaging, the implementation of single-photon emission computed tomography (SPECT) has allowed increased image contrast and more accurate tracer localization. AREAS COVERED: Recent technological innovations in the field of BS are treated, with a particular focus on multi-field-of-view devices allowing to cover the entire scan length with a 3D acquisition (WB-SPECT/CT). In addition, the applications of cadmium zinc telluride/CzT detectors capable of converting gamma photons directly into electrical impulses (i.e. 'digital SPECT') are discussed. EXPERT OPINION: Initial clinical experiences indicate that WB-SPECT/CT is characterized by higher sensitivity, diagnostic accuracy, and increased confidence in image interpretation with respect to the 'old-fashioned' BS (planar images with or without a single field-of-view SPECT). Furthermore, CzT-based detectors, thanks to their superior sensitivity, might be helpful to implement fast acquisition protocols. Further studies are needed to better define the clinical impact of bone CzT WB-SPECT/CT on patients' management and outcome, as well as its cost-benefit ratio.

Molecular imaging findings for treatment resistant depression.

Approximately 40% of patients with major depressive disorder (MDD) had limited response to conventional antidepressant treatments, resulting in treatment-resistant depression (TRD), a debilitating subtype that yielded a significant disease burden worldwide. Molecular imaging techniques, such as positron emission tomography (PET) and single photon emission tomography (SPECT), can measure targeted macromolecules or biological processes in vivo. These imaging tools provide a unique possibility to explore the pathophysiology and treatment mechanisms underlying TRD. This work reviewed and summarized prior PET and SPECT studies to examine the neurobiology and treatment-induced changes of TRD. A total of 51 articles were included with supplementary information from studies for MDD and healthy controls (HC). We found that there were altered regional blood flow or metabolic activity in several brain regions, such as the anterior cingulate cortex, prefrontal cortex, insula, hippocampus, amygdala, parahippocampus, and striatum. These regions have been suggested to engage in the pathophysiology or treatment resistance of depression. There was also limited data to demonstrate the changes in the markers of serotonin, dopamine, amyloid, and microglia over some regions in TRD. Moreover, several observed abnormal imaging indices were linked to treatment outcomes, supporting their specificity and clinical relevance. To address the limitations of the included studies, we proposed that future studies needed longitudinal designs, multimodal approaches, and radioligands targeting specific neural substrates for TRD to evaluate their baseline and treatment-related alterations in TRD. Adequate data sharing and reproducible data analysis can facilitate advances in this field.

99mTc-MAA accumulation within tumor in preoperative lung perfusion SPECT/CT associated with occult lymph node metastasis in patients with clinically N0 non-small cell lung cancer.

BACKGROUND: 99mTc-MAA accumulation within the tumor representing pulmonary arterial perfusion, which is variable and may have a clinical significance. We evaluated the prognostic significance of 99mTc-MAA distribution within the tumor in non-small cell lung cancer (NSCLC) patients in terms of detecting occult nodal metastasis and lymphovascular invasion, as well as predicting the recurrence-free survival (RFS). METHODS: Two hundred thirty-nine NSCLC patients with clinical N0 status who underwent preoperative lung perfusion SPECT/CT were retrospectively evaluated and classified according to the visual grading of 99mTc-MAA accumulation in the tumor. Visual grade was compared with the quantitative parameter, standardized tumor to lung ratio (TLR). The predictive value of 99mTc-MAA accumulation with occult nodal metastasis, lymphovascular invasion, and RFS was assessed. RESULTS: Eighty-nine (37.2%) patients showed 99mTc-MAA accumulation and 150 (62.8%) patients showed the defect on 99mTc-MAA SPECT/CT. Among the accumulation group, 45 (50.5%) were classified as grade 1, 40 (44.9%) were grade 2, and 4 (4.5%) were grade 3. TLR gradually and significantly increased from grade 0 (0.009 ± 0.005) to grade 1 (0.021 ± 0.005, P < 0.05) and to grade 2-3 (0.033 ± 0.013, P < 0.05). The following factors were significant predictors for occult nodal metastasis in univariate analysis: central location, histology different from adenocarcinoma, tumor size greater than 3 cm representing clinical T2 or higher, and the absence of 99mTc-MAA accumulation within the tumor. Defect in the lung perfusion SPECT/CT remained significant at the multivariate analysis (Odd ratio 3.25, 95%CI [1.24 to 8.48], p = 0.016). With a median follow-up of 31.5 months, the RFS was significantly shorter in the defect group (p = 0.008). Univariate analysis revealed that cell type of non-adenocarcinoma, clinical stage II-III, pathologic stage II-III, age greater than 65 years, and the 99mTc-MAA defect within tumor as significant predictors for shorter RFS. However, only the pathologic stage remained statistically significant, in multivariate analysis. CONCLUSION: The absence of 99mTc-MAA accumulation within the tumor in preoperative lung perfusion SPECT/CT represents an independent risk factor for occult nodal metastasis and is relevant as a poor prognostic factor in clinically N0 NSCLC patients. 99mTc-MAA tumor distribution may serve as a new imaging biomarker reflecting tumor vasculatures and perfusion which can be associated with tumor biology and prognosis.

Quantitative assessment of 99mTc-methylene diphosphonate bone SPECT/CT for assessing bone metastatic burden and its prognostic value in patients with castration-resistant prostate cancers: initial results in a single-center retrospective study.

PURPOSE: To evaluate the prognostic value of the quantitative assessment of 99mTc-methylene diphosphonate (99mTc-MDP) bone SPECT/CT in castration-resistant prostate cancer (CRPC) patients with bone metastases. METHODS: A total of 103 patients who underwent 99mTc-MDP bone SPECT/CT imaging from the neck to the proximal femur were included. First, in 65 patients without bone metastases, the normal range of standardized uptake value (SUV) of non-pathological bone was evaluated to determine an SUV threshold to reliably exclude most normal osseous activity. Then, in 38 CRPC patients with bone metastases, lesion uptake volume (LUV), which is the extracted volume of bone metastases exhibiting high accumulation above the SUV threshold, was calculated. The relation between LUV and prostate-related mortality was statistically evaluated. RESULTS: Based on the SUV measurements of non-pathological bones, the optimal SUV threshold, which defines abnormal bone SPECT uptake, was determined to be 8. Median LUV was 39 mL (interquartile range 4.0-104.3 mL) in the CRPC subjects with bone metastases. Kaplan-Meier survival analysis showed a significant relation between prostate cancer-specific survival and LUV (cut-off value, 19.95 mL; P = 0.001). Multivariate analysis revealed LUV as an independent prognostic factor for the survival (P = 0.008, hazard ratio 23.424). Global chi-square test showed that LUV had significant incremental prognostic value in addition to prostate-specific antigen and the interval from progression to CRPC until bone SPECT/CT (P = 0.022). CONCLUSION: Quantitative assessment of 99mTc-MDP bone SPECT images can provide valuable prognostic information in CRPC patients with bone metastases.

Radiomics and theranostics with molecular and metabolic probes in prostate cancer: toward a personalized approach.

INTRODUCTION: In the last decade, two new radionuclide-based therapies, 223Radichloride and radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA), have been approved by the regulatory authorities for the management of castrate-resistant prostate cancer (PCa). AREAS COVERED: The basic principles of PCa molecular imaging are illustrated, with a particular attention to the combined use of diagnosis and therapy in a unique approach (the so-called theranostics) for response prediction and assessment in patients submitted to 223Radichloride or PSMA targeted therapies. In this perspective, the potential of radiomics, an emerging discipline based on the extraction of quantitative features from medical images, is covered. EXPERT OPINION: Theranostic metabolic and molecular probes have been successfully applied to predict and monitor response to radionuclide-based therapies. In particular, both 99mTc-MDP and 18F-NaF resulted useful tools for personalized dosimetry and prognostic stratification before 223Ra-therapy, while PSMA-ligands, alone or in combination with 18F-FDG, provided valuable information to select patients who are more likely to benefit from RLT and getting information on PCa grade of differentiation and aggressiveness. In spite of its high potential, PET-radiomics for PCa is still at an embryonic phase and needs further validation.

Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles.

Nanoparticles are ultrafine particulate matter having considerable potential for treatment of central nervous system (CNS) disorders. Despite their tiny size, the blood-brain barrier (BBB) restricts their access to the CNS. Their direct cerebrospinal fluid (CSF) administration bypasses the BBB endothelium, but still fails to give adequate brain uptake. We present a novel approach for efficient CNS delivery of 111In-radiolabelled gold nanoparticles (AuNPs; 10-15 nm) via intra-cisterna magna administration, with tracking by SPECT imaging. To accelerate CSF brain influx, we administered AuNPs intracisternally in conjunction with systemic hypertonic saline, which dramatically increased the parenchymal AuNP uptake, especially in deep brain regions. AuNPs entered the CNS along periarterial spaces as visualized by MRI of gadolinium-labelled AuNPs and were cleared from brain within 24 h and excreted through the kidneys. Thus, the glymphatic-assisted perivascular network augment by systemic hypertonic saline is a pathway for highly efficient brain-wide distribution of small AuNPs.

Impact of atrial fibrillation on the cognitive decline in Alzheimer's disease.

BACKGROUND: Atrial fibrillation (AF) is a strong risk factor for Alzheimer's disease (AD) independent of ischemic stroke. However, the clinicopathological impact of AF on the severity of AD has not been well elucidated. We aimed to investigate the clinical differences between dementia patients with AF and those without AF by means of imaging data. METHODS: Following approval from the institutional ethics committee, patients with newly diagnosed AD or amnestic mild cognitive impairment (aMCI) were retrospectively screened (n = 170, 79.5 ± 7.4 years old). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Based on the MRI data, the cerebral volume, cerebral microbleeds (CMBs), periventricular white matter lesions (WMLs), and deep WMLs were evaluated. The regional cerebral blood flow (rCBF) was measured using 123I-IMP SPECT. RESULTS: Of the patients, 14 (8.2%) and 156 (91.8%) had AF (AF group) and sinus rhythm (SR group), respectively. The AF group had significantly lower MMSE scores than the SR group (average [standard deviation (SD)]: 19.4 [4.4] and 22.0 [4.4], respectively; p = 0.0347). Cerebral volume and CMBs did not differ between the two groups. The periventricular WMLs, but not the deep WMLs, were significantly larger in the AF group than in the SR group (mean [SD] mL: 6.85 [3.78] and 4.37 [3.21], respectively; p = 0.0070). However, there was no significant difference in rCBF in the areas related to AD pathology between the two groups. CONCLUSION: AD and aMCI patients with AF showed worse cognitive decline along with larger periventricular WMLs compared to those with SR, although the reduction of rCBF was not different between patients with AF and SR. The white matter lesions may be a more important pathology than the impairment of cerebral blood flow in dementia patients with AF. A larger study is needed to confirm our findings in the future.