Brain metabolic changes in patients with disseminated malignant melanoma under immunotherapy.

Although there is evidence that chemotherapy can have side effects on metabolism and brain function, there are few studies on the occurrence of these side effects with immunotherapy. The present study was conducted to assess whether brain metabolic changes occur in patients with malignant melanoma under immunotherapy. Thirty-nine patients after surgical intervention and with a diagnosis of malignant melanoma were retrospectively included and were divided into two groups: one group under the first-line therapy with anti-programmed cell death-1 ± anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies and the other group without any treatment after surgery, which served as a control. Basal and follow-up whole body and brain 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F]FDG) PET/computed tomography (CT) studies were performed. Changes in brain glucose metabolism after treatment initiation of the immunotherapy group were compared with the findings in the control group. In addition, longitudinal regression analysis to investigate whether the time under immunotherapy influenced the changes of brain metabolism was performed. None of the patients presented cognitive impairment or other neurological alterations between basal and follow-up brain [ 18 F]FDG PET/CT examinations. The statistical analysis revealed a significant relative SUV (SUVr)-loss in the left frontal region in patients of the immunotherapy group compared with the control group, with radjusted = -0.62 and P = 0.008. Severity of SUVr-loss was correlated with duration of treatment. Patients with disseminated malignant melanoma receiving immunotherapy may present a decrease of brain metabolism in the left frontal region, which is related with time-under-treatment, without any clinical evidence of neurological disorder.

Digital PET vs Analog PET: Clinical Implications?

Positron emission tomography (PET) is a functional imaging technique introduced in 1970s. Over the years, PET was used alone but is in 2000 when the first hybrid PET/CT device was clinically introduced. Since then, PET has continuously been marked by technological developments, being the most recent one the introduction of silicon photomultipliers (SiPMs) as an alternative to standard photomultiplier tubes used in analog PET/CT systems. SiPMs, the basis for the so called digital PET/CT systems, are smaller than standard photomultiplier tubes (enabling higher spatial resolution) and provide up to 100% coverage of the crystal area, as well as high sensitivity, low noise, and fast timing resolution. SiPMs in combination with optimized acquisition and reconstruction parameters improve the localization of the annihilation events, provide high definition PET images, and offer higher sensitivity and higher diagnostic performance. This article summarizes the evidence about the superior performance of the state of the art digital PET and highlights its potential clinical implications. Digital PET opens new perspectives in the quantification and characterization of small lesions, which are mostly undetectable using analog PET systems, potentially changing patient management and improving outcomes in oncological and non-oncological diseases. Moreover, digital PET offers the possibility to reduce radiation dose and scan times which may facilitate the implementation of PET to address unmet clinical needs.

"The added value of 18f-FDG PET/CT in the assessment of onset and steroid resistant polimyalgia rheumatica".

PMR is a common inflammatory rheumatic disease. Although its clinical characteristics are fully recognized, no specific test for its diagnosis has been established to date. Several studies have described a wide variety of diseases that present with polymyalgic symptoms. A 18FDG-PET/CT scan could help to deal with these differential diagnoses. The goal of our study is to describe the findings of the 18FDG-PET/CT scan in a cohort of PMR patients and to detail how the 18FDG-PET/CT scan improves accuracy when diagnosing other underlying conditions. This cross-sectional study enrolled patients with a diagnosis of PMR who underwent to a 18FDG-PET/CT scan to rule out other diagnosis. The 18FDG-PET/CT scan was performed either following clinical criteria at the onset of clinical symptoms or when the patient became PMR steroid resistant. Patients' demographic, clinical and analytical data at the moment of the 18FDG-PET/CT scan were recorded. The final diagnosis was confirmed according to clinical judgement. A total of 103 patients with PMR were included. In 49.51% of patients, the 18FDG-PET/CT scan was ordered to study resistance to steroid therapy. The final diagnoses of patients were PMR in 70.9% patients, large vessel vasculitis in 15.5%, neoplasms 4.8% and another diagnosis in the rest. The 18FDG-PET/CT scan is a very useful technique for the study of Polymyalgia Rheumatica, not only to help in the diagnostic process, but also due to its role in the identification of a variety of PMR-like patrons.

Extrastriatal SPECT-DAT uptake correlates with clinical and biological features of de novo Parkinson's disease.

Striatal dopamine transporter (DAT) uptake assessment through I123-Ioflupane Single-Pphoton Emission Computed Tomography (SPECT) provides valuable information about the dopaminergic denervation occurring in Parkinson's disease (PD). However, little is known about the clinical or biological relevance of extrastriatal DAT uptake in PD. Here, from the Parkinson's Progression Markers Initiative, we studied 623 participants (431 PD and 192 healthy controls) with available SPECT data. Even though striatal denervation was undoubtedly the imaging hallmark of PD, extrastriatal DAT uptake was also reduced in patients with PD. Topographically, widespread frontal but also temporal and posterior cortical regions showed lower DAT uptake in PD patients with respect to healthy controls. Importantly, a longitudinal voxelwise analysis confirmed an active one-year loss of extrastriatal DAT uptake within the PD group. Extrastriatal DAT uptake also correlated with the severity of motor symptoms, cognitive performance, and cerebrospinal fluid α-synuclein levels. In addition, we found an association between the Catechol-O-methyltransferase val158met genotype and extrastriatal DAT uptake. These results highlight the clinical and biological relevance of extrastriatal SPECT-DAT uptake in PD.

Digital versus analog PET/CT in patients with known or suspected liver metastases.

AIM: To assess if digital PET/CT improves liver lesion detectability compared to analog PET/CT in patients with known or suspected liver metastases. MATERIALS AND METHODS: We prospectively included 83 cancer patients, with one or more of these conditions: history of liver metastases, clinical risk of having liver metastases or presence of suspected liver metastases on the first of the two PET/CTs. All patients were consecutively scanned on each PET/CT on the same day after a single [18F]fluorodeoxyglucose dose injection. The order of acquisition was randomly assigned. Three nuclear medicine physicians assessed both PET/CTs by counting the foci of high uptake suspicious of liver metastases. Findings were correlated with appropriate reference standards; 19 patients were excluded from the analysis due to insufficient lesion nature confirmation. The final sample consisted of 64 patients (34 women, mean age 68 ± 12 years). RESULTS: As per-patient analysis, the mean number of liver lesions detected by the digital PET/CT (3.84 ± 4.25) was significantly higher than that detected by the analog PET/CT (2.91 ± 3.31); P < 0.001. Fifty-five patients had a positive PET/CT study for liver lesions. In 26/55 patients (47%), the digital PET/CT detected more lesions; 7/26 patients (27%) had detectable lesions only by the digital system and had <10 mm of diameter. Twenty-nine patients had the same number of liver lesions detected by both systems. In nine patients both PET/CT systems were negative for liver lesions. CONCLUSION: Digital PET/CT offers improved detectability of liver lesions over the analog PET/CT in patients with known or suspected liver metastases.

Identificación de adenomas ocultos en hiperparatiroidismo primario con PET-TC 18F-fluorocolina / Identification of Occult Adenomas in Primary Hyperparathyroidism With 18F-fluorocholine PET/CT

INTRODUCCIÓN: La principal causa de hiperparatiroidismo primario en nuestro medio es el adenoma paratiroideo único. La paratiroidectomía se considera el único tratamiento potencialmente curativo y requiere de estudios de imagen de localización preoperatorios para un abordaje quirúrgico dirigido. En pacientes con negatividad en pruebas convencionales, la PET-TC colina ha demostrado tasas de sensibilidad superiores respecto al gold-standard. MÉTODOS: Se diseñó un estudio de cohortes prospectivo que incluyó a 34 pacientes con diagnóstico de hiperparatiroidismo primario entre 2017 y 2019, candidatos a cirugía con pruebas de imagen con gammagrafía y SPECT-TC MIBI negativas. A todos se les realizó una PET-TC con 18F-fluorocolina. Los resultados se compararon con un grupo control de 30 pacientes con pruebas convencionales positivas intervenidos en el mismo período. RESULTADOS: La PET-TC colina detectó tejido paratiroideo hiperfuncionante en el 85% de los pacientes con gammagrafía previa negativa. Se realizó resección selectiva del adenoma identificado en estos pacientes, con criterio de curación en el 87% de los casos, sin precisar de exploración cervical bilateral. Los niveles de PTH, calcemia y el peso glandular fueron significativamente menores en este grupo con respecto al control. No se identificaron diferencias respecto al criterio de curación ni a la vía de abordaje en ambos grupos. CONCLUSIÓN: En nuestro estudio, la PET-TC colina demostró tasas superiores de detección que permitieron aumentar el número de pacientes candidatos a cirugía dirigida con disminución de la morbilidad quirúrgica, especialmente en grupos con adenomas de menor tamaño asociados a niveles más bajos de calcemia y PTH preoperatorias y en pacientes con cirugías cervicales previas

INTRODUCTION: Single parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHP) in our population. Parathyroidectomy is still the only potentially curative treatment and requires preoperative localization imaging studies to perform selective surgery. In patients with negative results on conventional tests, PET/CT has demonstrated higher sensitivity rates. METHODS: A prospective cohort study was designed, including 34 patients diagnosed with PHP between 2017 and 2019, candidates for surgery with negative preoperative localization tests with scintigraphy and MIBI SPECT/CT. All patients underwent PET/CT with 18F-Fluorocholine. The clinical, biochemical and postoperative outcome results were compared with a control group of 30 patients with positive standard tests. RESULTS: Hyperfunctional parathyroid tissue was detected in 85% of the patients that had undergone choline PET/CT. The selective resection of the adenoma identified in these patients achieved curative criteria in 87% of the cases without undergoing bilateral cervical surgical exploration. The preoperative levels of PTH, calcemia and gland weight were significantly lower in this group compared to the control group. No differences were identified in cure criteria or approach between the 2 groups. CONCLUSION: In our study, choline PET/CT showed higher detection rates compared to the gold standard. The increase provides the opportunity to perform unilateral selected adenoma resection, especially in patients with smaller adenomas associated with lower calcemia and PTH levels and patients with previous cervical surgery

Future Challenges of Multimodality Imaging.

During the last decade, positron emission tomography/computed tomography (PET/CT) and single-photon emission computed tomography/computed tomography (SPECT/CT) have procured advances in research and clinical application of fusion imaging. The recent introduction of digital PET/CT opens new horizons for multimodality molecular imaging. This system offers more precise, simultaneous morphologic, functional, and molecular information of a living system. Moreover, other combinations of anatomic and functional imaging modalities hold promise in basic medical research or in clinical medicine. These developments are paralleled by advances in the field of biomolecules and particles that will provide new agents useful for more than one imaging modality and will facilitate the study of the same target by different imaging devices. Digital PET/CT may emerge as a powerful multimodality technique with great clinical impact on the diagnosis and therapy assessment of oncological diseases due to its enhanced sensitivity.

Correction to: Superior performance of 18F-fluorocholine digital PET/CT in the detection of parathyroid adenomas.

The correct administered activity of 18F-FCH is 0.1-0.14 mCi/Kg, which is equivalent to 3.7-5.2 MBq/kg.

The Added Value of Tau-PET in the Assessment of Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is rare neurodegenerative disorder characterized by deposition of fibrillar aggregates of 4R tau-protein in neurons and glial cells. This disorder is underdiagnosed due to the overlap of the clinical syndrome with other related conditions. The clinical manifestations include cognitive impairment associated with behavioral changes, akinetic rigid syndrome, and prominent oculomotor dysfunction. We present the F-FDG and F-THK5351 PET images of a 71-year-old man diagnosed of probable PSP. This image highlights the hopeful results of the new tau-PET ligands radiotracers, because it allows to assess the distribution of tau-protein over time, closely associated with neurodegeneration in PSP.

Identification of Occult Adenomas in Primary Hyperparathyroidism With 18F-fluorocholine PET/CT. / Identificación de adenomas ocultos en hiperparatiroidismo primario con PET-TC 18F-fluorocolina.

INTRODUCTION: Single parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHP) in our population. Parathyroidectomy is still the only potentially curative treatment and requires preoperative localization imaging studies to perform selective surgery. In patients with negative results on conventional tests, PET/CT has demonstrated higher sensitivity rates. METHODS: A prospective cohort study was designed, including 34 patients diagnosed with PHP between 2017 and 2019, candidates for surgery with negative preoperative localization tests with scintigraphy and MIBI SPECT/CT. All patients underwent PET/CT with 18F-Fluorocholine. The clinical, biochemical and postoperative outcome results were compared with a control group of 30 patients with positive standard tests. RESULTS: Hyperfunctional parathyroid tissue was detected in 85% of the patients that had undergone choline PET/CT. The selective resection of the adenoma identified in these patients achieved curative criteria in 87% of the cases without undergoing bilateral cervical surgical exploration. The preoperative levels of PTH, calcemia and gland weight were significantly lower in this group compared to the control group. No differences were identified in cure criteria or approach between the 2groups. CONCLUSION: In our study, choline PET/CT showed higher detection rates compared to the gold standard. The increase provides the opportunity to perform unilateral selected adenoma resection, especially in patients with smaller adenomas associated with lower calcemia and PTH levels and patients with previous cervical surgery.

Superior performance of 18F-fluorocholine digital PET/CT in the detection of parathyroid adenomas.

OBJECTIVE: To compare detectability of hyperfunctioning parathyroid tissue (HPT) by digital and analog 18F-fluorocholine PET/CT in patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT. MATERIALS AND METHODS: Thirty-three patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT were prospectively included. All patients accepted to be scanned by digital and analog PET/CT in the same imaging session after a single injection of 18F-fluorocholine. Three nuclear medicine physicians evaluated the digital and analog PET/CT datasets to assess the detection rate of HPT. Maximum standard uptake values (SUVmax) of HPT and locoregional lymph nodes were measured in both systems. RESULTS: HPT was detected in 30/33 patients by the digital system, whereas it was detected in 22/33 patients by the analog system (p < 0.01). Moreover, in 21 of these 33 patients, both systems detected one focal 18F-fluorocholine uptake, and in one patient the digital system detected two foci. Histopathology demonstrated HPT in 32 patients and it was inconclusive in one patient. The digital PET/CT detected HPT in 29 of the 32 patients, and the analog system in 22 of the 32 (p < 0.01). All HPT suspected lesions resected and detected only by the digital system (n = 8) were < 10 mm (7.5 ± 1.3 mm), while those detected by both systems (n = 22) were > 10 mm (13 ± 3.8 mm). SUVmax of HPT lesions was significantly higher than SUVmax of locoregional lymph node independently of the PET/CT system used (4.5 ± 1.9 vs. 2.9 ± 1.3, p < 0.0001). CONCLUSIONS: Digital PET/CT offers superior performance over analog system in patients with suspected HPT and previous negative/inconclusive imaging examinations, particularly in sub-centimeter lesions. SUVmax can help in the differentiation between HTP and locoregional lymph nodes.

Correction to: Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions.

The article Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions, written by Francisco Fuentes-Ocampo, Diego Alfonso López-Mora, Albert Flotats, Gabriela Paillahueque.

Comparison of image quality and lesion detection between digital and analog PET/CT.

OBJECTIVE: The purpose of this study was to compare image quality and lesion detection capability between a digital and an analog PET/CT system in oncological patients. MATERIALS AND METHODS: One hundred oncological patients (62 men, 38 women; mean age of 65 ± 12 years) were prospectively included from January-June 2018. All patients, who accepted to be scanned by two systems, consecutively underwent a single day, dual imaging protocol (digital and analog PET/CT). Three nuclear medicine physicians evaluated image quality using a 4-point scale (-1, poor; 0, fair; 1, good; 2, excellent) and detection capability by counting the number of lesions with increased radiotracer uptake. Differences were considered significant for a p value <0.05. RESULTS: Improved image quality in the digital over the analog system was observed in 54% of the patients (p = 0.05, 95% CI, 44.2-63.5). The percentage of interrater concordance in lesion detection capability between the digital and analog systems was 97%, with an interrater measure agreement of κ = 0.901 (p < 0.0001). Although there was no significant difference in the total number of lesions detected by the two systems (digital: 5.03 ± 10.6 vs. analog: 4.53 ± 10.29; p = 0.7), the digital system detected more lesions in 22 of 83 of PET+ patients (26.5%) (p = 0.05, 95% CI, 17.9-36.7). In these 22 patients, all lesions detected by the digital PET/CT (and not by the analog PET/CT) were < 10 mm. CONCLUSION: Digital PET/CT offers improved image quality and lesion detection capability over the analog PET/CT in oncological patients, and even better for sub-centimeter lesions.

Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions.

PURPOSE: The purpose of this study was to assess whether digital photon counting technology in digital PET/CT influences the quantification of SUVmax in target lesions and regions of reference compared to analog PET/CT before an interchangeable use of either system in follow up studies. METHODS: From January to June of 2018, 100 oncological patients underwent successive PET/CT imaging with digital and analog systems in the same day. Fifty-eight patients underwent analog imaging first and digital imaging thereafter, and 42 patients the other way round. SUVmax was measured in reference regions (liver and mediastinal blood pool) and in the most metabolically active target lesion in each patient. According to the sequence order of PET/CT acquisition, two groups of SUVmax values were obtained, i.e. group 1: analog PET/CT performed first; group 2: digital PET/CT performed first. RESULTS: Mean SUVmax in the total sample (regardless of the order of PET/CT acquisition) in the target lesions with the analog PET/CT was 8.14 ± 6.39 and the digital 9.97 ± 6.14 (P = 0.000). Total mean SUVmax in the liver with the analog was 4.39 ± 2.59 and the digital 4.46 ± 3.18 (P = 0.477). Total mean SUVmax in the mediastinal blood pool with the analog was 2.30 ± 0.67 and the digital 2.54 ± 0.74 (P = 0.000). Group 1: mean SUVmax in the target lesions with the analog system was 6.64 ± 4.71 and the digital 9.48 ± 5.60 (P = 0.000). Mean liver SUVmax with the analog was 4.70 ± 2.90 and the digital 4.80 ± 3.72 (P = 0.088). Mediastinal blood pool SUVmax with the analog was 2.33 ± 0.66 and the digital 2.45 ± 0.73 (P = 0.041). Group 2: mean SUVmax in target lesions with the digital system was 10.63 ± 6.88 and the analog 10.16 ± 7.76 (P = 0.046). Mean liver SUVmax with the digital was 3.99 ± 2.20 and the analog 3.96 ± 2.04 (P = 0.218). Mediastinal blood pool SUVmax with the digital was 2.66 ± 0.75 and the analog 2.27 ± 0.68 (P = 0.000). No significant differences between both time delays were found. CONCLUSIONS: Improved photon counting technology in the digital PET/CT, and the effect of delayed increased uptake and retention significantly increases SUVmax values. This has to be taken into account before interchangeable use of either system in follow up studies.

Cortical atrophic-hypometabolic dissociation in the transition from premanifest to early-stage Huntington's disease.

PURPOSE: Huntington's disease (HD) is a fatal neurodegenerative disorder with no effective treatment currently available. Although the pathological hallmark of HD is massive striatal atrophy, it has been suggested that cortical deterioration may concomitantly occur and play a major role in the patient's functional independence. Our objective was to characterize cortical structural and metabolic neurodegeneration in the transition from premanifest to early-stage Huntington's disease (HD). METHODS: Using a surface-based neuroimaging approach, we compared cortical thickness and intracortical FDG-PET uptake in 19 early-symptomatic HD patients with respect to 21 premanifest HD individuals. RESULTS: Early-HD patients showed significant cortical atrophy and intracortical hypometabolism when compared to premanifest subjects (p < 0.05, corrected for multiple comparisons). However, whereas the atrophy pattern was restricted to precentral and parieto-occipital regions, a pronounced frontotemporal hypometabolism was observed. Importantly, structural changes correlated with motor and cognitive performance, and metabolic changes were associated with the presence and severity of apathy in this population, a core neuropsychiatric feature of this disorder. CONCLUSION: Our findings reveal an asynchronous neuronal loss and metabolic compromise across the cerebral cortex in early HD. Hence, the use of structural and metabolic imaging indicators to characterize disease progression in this population should take into consideration the dissociation which occurs between cortical atrophy and hypometabolism.

The impact of bilingualism on brain structure and function in Huntington's disease.

INTRODUCTION: Bilingualism exerts neuroprotective effects against neurodegeneration. In Huntington's disease (HD), the systems involved in bilingual control show early compromise, but the effect of bilingualism on the course of HD is unknown. METHODS: We addressed the impact of livelong use of bilingualism on the clinical features, brain structure and function in 30 early-mild stage HD patients. Using voxel-wise regression analysis, we explored the effect of levels of use of bilingualism on grey-matter volume (GMV) and 18F-FDG metabolism. RESULTS: Higher use of bilingualism was associated with better performance in inhibitory control and set-shifting independently of age and education and with higher GMV in the inferior frontal gyrus. 18F-FDG data revealed a significant effect on multiple fronto-temporal regions, specifically, in the dorsal anterior cingulate cortex, the anterior insula, the ventromedial orbital prefrontal cortex and the inferior frontal gyrus. These changes contributed to better inhibitory control and set-shifting and to more preserved motor and functional capacity. CONCLUSION: In HD, lifelong use of bilingualism is associated with structural and metabolic brain changes that have an impact on cognition, movement and functionality. These findings highlight the importance of stimulating cognitive and brain reserve in HD and in other neurodegenerative conditions.