Towards improved diagnosis: radiomics and quantitative biomarkers in 18F-PSMA-1007 and 18F-fluorocholine PET/CT for prostate cancer recurrence.

OBJECTIVE: This study compared the radiomic features and quantitative biomarkers of 18F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. METHODS: A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUVmean, PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. RESULTS: Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUVmax value was significantly higher for 18F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P < 0.001). There were statistically significant differences in median SUVmean, TL-PSMA/FCH, and PSMA/FCH-TV as per table 2 between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P < 0.001). The correlation between SUVmean/SUVmax and PSA level was moderate, both for 18F-PSMA (r = 0.44, P < 0.001; r = 0.44, P < 0.001) and FCH (r = 0.35, P < 0.001; r = 0.41, P < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18F-PSMA (r = 0.56, P < 0.001; r = 0.57, P < 0.001) and FCH (r = 0.49, P < 0.001; r = 0.51, P < 0.001). While patients who received hormone therapy showed higher median SUVmax values for both radiotracers compared with those who did not, the difference was statistically significant only for 18F-PSMA (P < 0.05). CONCLUSION: Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.

Dose optimization of 2D X-ray image acquisition protocols in image-guided radiotherapy.

PURPOSE: In contemporary radiotherapy, patient positioning accuracy relies on kV imaging. This study aims at optimizing planar kV image acquisition protocols regarding patient dose without degrading image quality. MATERIALS AND METHODS: An image quality test-object was placed in-between PMMA plates, suitably arranged to model head or pelvis. Constructed phantoms were imaged using default protocols, the resultant image quality was assessed and the corresponding radiation dose was measured. The process was repeated using numerous kV/mAs combinations to identify those acquisition settings providing images at lower dose than the default protocols but without deterioration in image quality. Default and dose-optimized protocols were then tested on an anthropomorphic phantom and on 51 patients during two successive treatment sessions. Image quality was independently assessed by two readers. Organ and effective doses were estimated using a Monte Carlo simulation software. RESULTS: Low-contrast detectability exhibited a stronger dependence on kV/mAs settings, compared to high-contrast resolution. Dose-optimized protocols resulted in significant dose reductions (anteroposterior-head 48.0 %, lateral-head 30.0 %, anteroposterior-pelvis 28.4 %, lateral-pelvis 27.0 %) compared to the default ones, without compromising image quality. Optimized protocols decreased effective doses by 54 % and 29.6 % in head and pelvic acquisitions, respectively. Regarding image quality, anthropomorphic and patient images acquired using the dose-optimized protocols were subjectively evaluated equivalent to those obtained with the corresponding default settings, indicating that the proposed protocols may be routinely used. CONCLUSIONS: Given the potentially large number of radiotherapy fractions and the pertinent image acquisitions, dose-optimized protocols could significantly reduce patient dose associated with planar imaging without compromising positioning accuracy.

Organizing and operating a one day clinic / theragnostic center.

The increasing success of recent nuclear medicine therapies, which followed the NETTER-1 and VISION trials, has boosted the interest for setting up and operating theragnostic centers. EANM, SNMMI and IAEA have recently published a joint guideline in order to assist nuclear medicine centers towards that path. The present paper will focus on the main points of these guidelines, with reference to the Greek radiation protection legislation.

Spleen visualization in both TTR and AL amyloidosis during 99mTc-DPD scintigraphy. Do we have to deal with a different than the myocardial uptake mechanism?

Technetium-99m- diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) is currently used in Europe for the diagnosis of cardiac amyloidosis, being able to distinguish light chain (AL) from transthyretin (TTR) type. We are reporting obvious spleen visualization in two patients suffering the first from proven TTR and the second from AL type of cardiac amyloidosis, with myocardial uptake-as anticipated-only in the first one. We raise the hypothesis that a common uptake mechanism exists for the spleen amyloid regardless of the type of the disease (AL or TTR), and is possibly different than the cardiac uptake mechanism.

EFOMP policy statement 18: Medical physics education for the non-physics healthcare professions.

Although Medical Physics educators have historically contributed to the education of the non-physics healthcare professions, their role was not studied in a systematic manner. In 2009, EFOMP set up a group to research the issue. In their first paper, the group carried out an extensive literature review regarding physics teaching for the non-physics healthcare professions. Their second paper reported the results of a pan-European survey of physics curricula delivered to the healthcare professions and a Strengths-Weaknesses-Opportunities-Threats (SWOT) audit of the role. The group's third paper presented a strategic development model for the role, based on the SWOT data. A comprehensive curriculum development model was subsequently published, whilst plans were laid to develop the present policy statement. This policy statement presents mission and vision statements for Medical Physicists teaching non-physics users of medical devices and physical agents, best practices for teaching non-physics healthcare professionals, a stepwise process for curriculum development (content, method of delivery and assessment), and summary recommendations based on the aforementioned research studies.

Differentiated thyroid cancer: Case report of false positive 131I uptake on whole body scintigraphy in a patient with bilateral femur osteonecrosis.

OBJECTIVE: Differentiated thyroid cancer (DTC) is one of the fastest growing cancers worldwide. Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, exhibiting a more aggressive behavior. Radioiodine whole-body scintigraphy (WBS) has been used in the detection of DTC. Radioiodine is a sensitive marker for detection of thyroid cancer; however, radioiodine uptake is not specific for thyroid tissue. It can also be seen in healthy tissue as well as in inflammation, or in a variety of benign and malignant non-thyroidal entities. SUBJECT AND METHODS: The subject of the present case report is a 52 years old man with brain metastatic DTC who received radioiodine therapy and corticosteroids as palliative therapy. Whole-body scintigraphy revealed bilateral iodine uptake of the femur. Corticosteroid therapy is among the most widely recognized risk factor for osteonecrosis, which at the present case had to be recognized as a false positive (iodine-131) 131I uptake in order to avoid diagnostic error. RESULTS: Post therapeutic whole body scintigraphy revealed no uptake in the thyroid bed as well as pathologic uptake of radioiodine in both femurs. The magnetic resonance imaging (MRI) of the femurs combined with the history of long term exposition on high doses of corticosteroids evidenced diagnosis of steroid-induced osteonecrosis of the femurs. CONCLUSION: Radioiodine WBS plays an important role in clinical decision making for the evaluation and the management of patients with DTC. Despite its high range of sensitivity and specificity, a variety of reports of false positive whole body scans has demonstrated a diversity of causes. Comprehension of the physiology of iodine uptake and of the pathophysiology of clinical entities which end up giving false positives scans, provides clinicians a useful tool in order to avoid diagnostic and therapeutic errors as far as DTC is concerned.

Unusually seen pattern of 99mTc-DPD soft tissue uptake in a patient with AL amyloidosis. Is it an amyloid type indicator in specific cases?

Technetium-99m (99mTc)-labeled pyrophosphate (PYP) and 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) are currently the most established imaging agents for the diagnosis of cardiac amyloidosis, being able to distinguish light chain (AL) from transthyretin (TTR) type of the disease. We present a pattern of increased uptake in all soft tissues, sparing the organs that are usually most affected.

Could the Majority of the Greek and Cypriot Population Be Vitamin D Deficient?

OBJECTIVE: Hypovitaminosis D is prevalent in epidemic proportions in many developed countries. The aim of this study is to investigate the prevalence of adequate 25-hydroxyvitamin D [25(OH)D] levels in two Mediterranean countries, Greece and Cyprus. METHODS: Data such as 25(OH)D, the month of blood sample collection, and demographic information were blindly collected from 8780 Greek and 2594 Cypriot individuals over 5 years. Comorbidities were also recorded for 839 Greek subjects. Univariate and multivariate analyses were used to examine the relationship between these variables and 25(OH)D levels. RESULTS: In the samples studied, 72.7% of the Greek and 69.3% of the Cypriot population sample had inadequate levels of 25(OH)D. The mean level for the Greek subjects was 25.1 ng/mL and for Cypriots 25.8 ng/mL. For both samples, only month and gender were significantly associated with 25(OH)D levels, and the highest mean levels were recorded in September. For the recorded diseases, the lowest levels were recorded in sickle cell anaemia 13.6 ± 10.2 ng/mL, autoimmune diseases 13.0 ± 8.4 ng/mL, and cancer 22.6 ± 9.5 ng/mL. CONCLUSIONS: The prevalence of vitamin D deficiency is paradoxically high in both Mediterranean countries.

A novel quantitative method for assessing the therapeutic response to Tafamidis therapy in patients with cardiac TTR amyloidosis. A preliminary report.

OBJECTIVE: Cardiomyopathy is a common manifestation of transthyretin amyloidosis (ATTR), leading to heart failure, associated with high morbidity and mortality. The aim of this study was to investigate the effect of Tafamidis treatment by means of cardiac radiotracer uptake on myocardial scintigraphy. SUBJECTS AND METHODS: Five male patients, mean age 76.2 years, with wild-type ATTR were included in the protocol. Total body scanning using technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) (in four patients) and technetium-99m-hydroxymethylene diphosphonate (99mTc-HMDP) (in one) was performed pre- and one year post-Tafamidis therapy. A novel quantitation method for assessing radiotracer cardiac uptake was employed. The geometric mean was computed for both cardiac and thigh region of interest (ROI) and the heart-to-thigh (HtT) ratio was assessed by dividing the corresponding geometric mean counts. RESULTS: Heart-to-thigh ratio was improved (decreased) in four of the patients receiving Tafamidis, in keeping with lower uptake to the cardiac region. These patients also demonstrated a relatively favorable clinical response to Tafamidis. The patient evaluated by 99mTc-HMDP exhibited minimal HtT ratio reduction and stable clinical and echocardiographic characteristics. CONCLUSION: Sequential HtT ratio measurements could potentially identify patients with a favorable response to Tafamidis treatment at earlier stages, compared to other imaging modalities or serological biomarkers.

SPECT analysis and language profile in Greek speaking patients with subtypes of frontotemporal dementia.

OBJECTIVE: We aimed to examine if single photon emission computed tomography (SPECT) can discriminate between variants of frontotemporal dementia (FTD). As a secondary investigation we identify and establish the linguistic differences between those variants. MATERIALS AND METHODS: Nine patients with semantic variant primary progressive aphasia (svPPA), 8 with non-fluent variant primary progressive aphasia (nfvPPA) and 17 with behavioral variant of frontotemporal dementia (bvFTD) were compared on Addenbrooke's cognitive examination-revised (ACE-R), auditory comprehension, oral expression and verbal fluency. All patients were also compared with healthy controls. Patients were evaluated using technetium-99m-hexamethylproyleneamine oxime (99mTc-HMPAO) brain SPECT as a measure of regional cerebral flow. RESULTS: Significant group differences between all patients and controls were found for ACE-R, auditory comprehension and oral expression. Semantic variant primary progressive aphasia patients performed higher in letter compared to category fluency with significant deficits in auditory comprehension and oral expression. Non-fluent variant primary progressive aphasia patients showed significant deficits in auditory comprehension but not oral expression while performed lightly worse in letter fluency compared to category. Behavioral variant of frontotemporal dementia patients showed deficits in auditory comprehension and oral expression and performed similar in category and letter fluency. Single photon emission computed tomography analysis revealed left frontotemporal hypoperfusion extending to the right frontotemporal region in svPPA patients. Non-fluent variant primary progressive aphasia patients presented left frontotemporal hypoperfusion with participation of the left parietal and right frontotemporal regions. Behavioral variant of frontotemporal dementia patients showed bilateral frontotemporal hypoperfusion compared to parietal and visual cortices. CONCLUSION: Our findings suggest that SPECT may assist in the discrimination of the FTD variants. We also confirmed that bvFTD patients share similar language deficits with svPPA patients.

Institutional Diagnostic Reference Levels and Peak Skin Doses in selected diagnostic and therapeutic interventional radiology procedures.

PURPOSE: Institutional (local) Diagnostic Reference Levels for Cerebral Angiography (CA), Percutaneous Transhepatic Cholangiography (PTC), Transarterial Chemoembolization (TACE) and Percutaneous Transhepatic Biliary Drainage (PTBD) are reported in this study. MATERIALS AND METHODS: Data for air kerma-area product (PKA), air kerma at the patient entrance reference point (Ka,r), fluoroscopy time (FT) and number of images (NI) as well as estimates of Peak Skin Dose (PSD) were collected for 142 patients. Therapeutic procedure complexity was also evaluated, in an attempt to incorporate it into the DRL analysis. RESULTS: Local PKA DRL values were 70, 34, 189 and 54 Gy.cm2 for CA, PTC, TACE and PTBD respectively. The corresponding DRL values for Ka,r were 494, 194, 1186 and 400 mGy, for FT they were 9.2, 14.2, 27.5 and 22.9 min, for the NI they were 844, 32, 602 and 13 and for PSD they were 254, 256, 1598 and 540 mGy respectively. PKA for medium complexity PTBD procedures was 2.5 times higher than for simple procedures. For TACE, the corresponding ratio was 1.6. PSD was estimated to be roughly 50% of recorded Ka,r for procedures in the head/neck region and 10% higher than recorded Ka,r for procedures in the body region. In only 5 cases the 2 Gy dose alarm threshold for skin deterministic effects was exceeded. CONCLUSION: Procedure complexity can differentiate DRLs in Interventional Radiology procedures. PSD could be deduced with reasonable accuracy from values of Ka,r that are reported in every angiography system.

Applications of Convolutional Neural Networks in neurodegeneration and physiological aging.

The process of aging is linked with significant changes in a human's physiological organization and structure. This is more evident in the case of the brain whose functions generally vary between young and old individuals. Detecting such patterns can be of significant importance especially during the Mild Cognitive Impairment (MCI) stage which is a transition state before the clinical onset of dementia. Intervening in that stage may delay or eventually prevent dementia onset. In this paper we propose a new methodology based in electroencephalographic (EEG) recordings, aiming to classify individuals into healthy, pathological (patients diagnosed with MCI or Mild Dementia) and young, old groups (healthy individuals over and under 50 years of age) through functional connectivity and macro-architecture features. These features are calculated on the estimated brain region activations through the inverse problem solution, enabling us to transform the sensor level EEG recordings through an appropriate transformation matrix. Afterwards, Synchronization Likelihood and Relative Wavelet Entropy values were calculated along with the graph metrics corresponding to the functional connectivity values, as well as the relative energy contributions of five EEG bands (delta, theta, alpha, beta and gamma). These features were organized in Red, Green, Blue (RGB) image-like data structures. Therefore, it was possible to classify each individual into one of the two groups per experiment employing Convolutional Neural Networks. From the maximum classification accuracy achieved on the test set, 90.48% for the pathological aging group and 91.19% for the physiological aging, it is evident that the proposed approach is capable of providing adequate health and age group classification.

The consequences of COVID-19 pandemic in the routine of Nuclear Medicine Departments.

The outbreak and spreading of the COVID-19 pandemic have affected billions of people around the world, severely disrupting many aspects of their lives. Although not at the frontline of the pandemic response, Nuclear Medicine departments have to adopt their clinical routine to the new environment. A series of protective measures, including among others spatial arrangements to promote social distancing, meticulous hand hygiene and use of personal protective equipment, workload reduction, patient screening at admission and examination protocol adjustments, have to be adopted in order to minimize the risk of spreading the infection and ensure the safety of both their patients and staff. As the pandemic seems to slowly recede, the valuable experience gained should help everyone be much better prepared for a possible new outbreak.

Determination of the glomerular filtration rate in patients with type 2 diabetes: An assessment of the agreement between 51Cr-EDTA plasma clearance and 99mTc-DTPA plasma clearance, 99mTc-DTPA renography and plasma creatinine prediction equation.

AIMS: To investigate the agreement of glomerular filtration rate (GFR) determination between 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) plasma clearance (GFREDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance (GFRDTPA), the Gates 99mTc-DTPA renographic method (GFRGates) and the serum creatinine Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI, GFRSCr) in patients with type 2 diabetes mellitus (T2DM). METHODS: Ninety-nine T2DM patients underwent GFR determinations simultaneously with 51Cr-EDTA and 99mTc-DTPA (using the slope-intercept technique and the Brochner-Mortensen correction) and also with GFRGates and GFRSCr. RESULTS: In the comparison between GFREDTA versus GFRDTPA, GFRGates and GFRSCr, the Bland-Altman statistic provided 0.0 ± 13.2, 17.4* ± 28.8 and -5.9* ± 30.1 (*p < 0.001 for the difference from 0). Lin's concordance correlation coefficient showed substantial (0.976), poor (0.737) and poor (0.872) agreement, respectively. The proportion of the index results within the 30% and 10% of GFREDTA measurements were 95% and 74% for GFRDTPA, 53% and 19% for GFRGates, and 83% and 26% for GFRSCr, respectively. CONCLUSION: In T2DM patients, a clinically acceptable agreement is demonstrated between 51Cr-EDTA and 99mTc-DTPA plasma clearance for GFR measurements, suggesting conditional interchangeability between those compounds. Both the CKD-EPI prediction equation and the Gates' renographic method cannot assess GFR reliably, the latter appearing less unfailing than the former.

The effect of scatter correction and radius of rotation on semiquantitative measurements in SPECT 123I-FP-CIT imaging. A phantom study.

PURPOSE: The high energy emissions of 123I and the suboptimal radius of rotation affect the semiquantitative measurements performed during 123I-FP-CIT tomographic imaging. An in-house extra low cost striatum phantom with brain and striatum compartments was constructed and was used to study the effects of Triple Energy Window scatter correction (TEW-SC) and radius of rotation on the Specific Binding Ratio (SBR) measurements. MATERIALS AND METHODS: The phantom compartments were filled with radioactive 123I solutions with varying concentrations, in a series of experiments. Tomographic images were acquired at six different radii of rotation, with and without TEW-SC and the SBRs were calculated using appropriate regions of interest, as in clinical imaging. RESULTS: SBRs decreased with increasing radius of rotation in both non-SC and TEW-SC images, the decrease being more pronounced in the latter. The application of TEW-SC increases SBR values by 40% on average. A maximum %Recovery of 42.7% of the true SBR value was achieved in the non-SC images, which increased to 64.6% after TEW-SC. Appropriate correction factors (CF) were calculated in order to make the SBR values independent on the radius of rotation, which could be used to correct SBR values obtained from tomographic acquisitions with suboptimal radius of rotation. CONCLUSION: The use of appropriate CF can provide more consistent SBR values and a more meaningful comparison between SBRs calculated from images acquired at different radii of rotation.

A study on the optimization of the administered activity in myocardial perfusion SPECT imaging with Tc-99m according to body measurements.

PURPOSE: Nuclear medicine myocardial perfusion imaging (MPI) in obese patients requires the administration of higher amounts of radioactivity, to compensate for the loss of photons due to the increased attenuation and scatter. The aim of the present study was to investigate whether an administered activity escalation protocol, proposed to yield the same effective dose irrespective of patient's weight, can also lead to images of comparable count density for all patients. MATERIALS AND METHODS: 184 pharmacologically induced stress 99m-Tc MIBI and 99m-Tc tetrofosmin SPECT MPI examinations (123 males, 61 females) were included in this study. Body weight, BMI and chest circumference were collected for each patient. The administered activity was adjusted to body weight according to the IAEA protocol. Detector count rate (DCR) from the projection images and normal myocardial count rate (MCR) from the appropriately segmented reconstructed images, with and without attenuation correction, were recorded. RESULTS: No statistically significant correlation was found between DCR and any anthropometric parameter. A weak correlation was observed between MCR and BMI and between MCR and chest circumference for male patients only, but even these correlations were eliminated after the application of attenuation correction. The anthropometric parameter that generally correlates more strongly with DCR/MBq and MCR/MBq was body weight for men and chest circumference for women. CONCLUSION: The IAEA activity escalation protocol used in this study leads to comparable image count densities, irrespective of body weight, for both men and women.

SmartHypnos: Developing a Toolbox for Polysomnographic Data Visualization and Analysis.

In this paper we present the first steps in developing SmartHypnos, an easy to use and user friendly graphical user interface, which aims to provide polysomngographic data visualization and the detection and classification of sleep related events. Currently SmartHypnos supports the visualization of EEG, ECG, EOG and EMG signals, and respiratory signals such as nasal pressure, thermistor, oxygen saturation, thoracic and abdominal belt recordings. All these are incorporated into an interface that provides quick and effortless access to the signals mentioned above. The interface displays automatic sleep staging capabilities as well as the detection of apnea events with accuracy rates surpassing 80%. It is expected that SmartHypnos will reduce the time required to analyze sleep data and also reduce possible human errors.

The effect of scatter correction on planar and tomographic semiquantitative 123I cardiac imaging. A phantom study.

OBJECTIVE: In cardiac I-123 (123I) imaging downscatter from high energy emissions degrades the image and introduces distortion of semi-quantitative analysis when using a low energy collimator. The effect of a triple energy window (TEW) scatter correction technique, using windows immediately above and below the principal window centered on 159keV, was examined. MATERIALS AND METHODS: A hemispherical cardiac phantom was inserted into a cylindrical phantom and both were filled with radioactive 123I water solutions. Phantoms were submitted to planar and tomographic scintigraphy under various acquisition and processing conditions, including the use of medium energy (ME) and low energy (LE) collimation. RESULTS: In planar imaging, there was a distance dependent count loss with the LEHR collimator which was partly restored with TEW correction. There was minimal dependence of count rate with distance in using ME collimation. Conversely, the heart to background (H/B) ratio increased with increasing distance with the LEHR collimator, but in applying the TEW correction that ratio paralleled the minimally affected values obtained with the ME collimation. In tomographic imaging the acquired H/B ratio was lower with LE collimation alone, in comparison to the ME collimator, but it was raised significantly when applying the TEW scatter correction. Quantitative measurements also depended on the background method and the reconstruction algorithm applied. CONCLUSION: In cardiac 123I imaging with a LE collimator the use of TEW scatter correction provides a semi-quantitative assessment comparable to that attained with ME collimation and may moderate inter-institutional inconsistencies.