Glucose uptake by individual skeletal muscles during running using whole-body positron emission tomography

The purpose of this study was to examine, by positron emission tomography (PET), the distribution of [18F]fluoro-deoxy-glucose ([18F]FDG) uptake by human muscles during 35 min of running. Thirteen healthy male subjects were studied, seven of whom participated in the exercise study. Running intensity was kept constant such that the subjects' heart rates were maintained at between 140 and 150 beats per minute. [18F]FDG [62.9 (14.8) MBq, mean (SD)] was injected after 15 min of running. PET imaging was started immediately after the running ended. The ratio of [18F]FDG uptake by muscles in runners to that in control subjects (r-c ratio) varied from three to six for the muscles of the foot and leg below the knee joint. The r-c ratio of the medial head of the gastrocnemius (MG) was higher than that of its lateral head (LG). The r-c ratio of the rectus femoris (RF) was lower than that of the other three muscles of the quadriceps femoris (QF). The r-c ratio of inactive muscles located above the waist was approximately 0.7. These results suggest that, during the moderate running of this study: (1) glucose uptake by muscles of the foot and leg below the knee joint clearly increases, (2) the r-c ratio differs significantly among the skeletal muscles, which act synergistically, and (3) glucose uptake by inactive skeletal muscles decreases.     

Pyruvate‐lactate exchange and glucose uptake in human prostate cancer cell models. A study in xenografts and suspensions by hyperpolarized [1‐13C]pyruvate MRS and [18F]FDG‐PET

Reprogramming of energy metabolism in the development of prostate cancer can be exploited for a better diagnosis and treatment of the disease. The goal of this study was to determine whether differences in glucose and pyruvate metabolism of human prostate cancer cells with dissimilar aggressivenesses can be detected using hyperpolarized [1‐¹³C]pyruvate MRS and [¹⁸F]FDG‐PET imaging, and to evaluate whether these measures correlate. For this purpose, we compared murine xenografts of human prostate cancer LNCaP cells with those of more aggressive PC3 cells. [1‐¹³C]pyruvate was hyperpolarized by dissolution dynamic nuclear polarization (dDNP) and [1‐¹³C]pyruvate to lactate conversion was followed by ¹³C MRS. Subsequently [¹⁸F]FDG uptake was investigated by static and dynamic PET measurements. Standard uptake values (SUVs) for [¹⁸F]FDG were significantly higher for xenografts of PC3 compared with those of LNCaP. However, we did not observe a difference in the average apparent rate constant k_pl of ¹³C label exchange from pyruvate to lactate between the tumor variants. A significant negative correlation was found between SUVs from [¹⁸F]FDG PET measurements and k_pl values for the xenografts of both tumor types. The k_pl rate constant may be influenced by various factors, and studies with a range of prostate cancer cells in suspension suggest that LDH inhibition by pyruvate may be one of these. Our results indicate that glucose and pyruvate metabolism in the prostate cancer cell models differs from that in other tumor models and that [¹⁸F]FDG‐PET can serve as a valuable complementary tool in dDNP studies of aggressive prostate cancer with [1‐¹³C]pyruvate.     

Drug‐induced cardiomyopathy: Characterization of a rat model by [18F]FDG/PET and [99mTc]MIBI/SPECT

BackgroundDrug‐induced cardiomyopathy is a significant medical problem. Clinical diagnosis of myocardial injury is based on initial electrocardiogram, levels of circulating biomarkers, and perfusion imaging with single photon emission computed tomography (SPECT). Positron emission tomography (PET) is an alternative imaging modality that provides better resolution and sensitivity than SPECT, improves diagnostic accuracy, and allows therapeutic monitoring. The objective of this study was to assess the detection of drug‐induced cardiomyopathy by PET using 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose (FDG) and compare it with the conventional SPECT technique with [^99mTc]‐Sestamibi (MIBI).MethodsCardiomyopathy was induced in Sprague Dawley rats using high‐dose isoproterenol. Nuclear [¹⁸F]FDG/PET and [^99mTc]MIBI/SPECT were performed before and after isoproterenol administration. [¹⁸F]FDG (0.1 mCi, 200‐400 µL) and [^99mTc]MIBI (2 mCi, 200‐600 µL) were administered via the tail vein and imaging was performed 1 hour postinjection. Isoproterenol‐induced injury was confirmed by the plasma level of cardiac troponin and triphenyltetrazolium chloride (TTC) staining.ResultsIsoproterenol administration resulted in an increase in circulating cardiac troponin I and showed histologic damage in the myocardium. Visually, preisoproterenol and postisoproterenol images showed alterations in cardiac accumulation of [¹⁸F]FDG, but not of [^99mTc]MIBI. Image analysis revealed that myocardial uptake of [¹⁸F]FDG reduced by 60% after isoproterenol treatment, whereas that of [^99mTc]MIBI decreased by 45%.ConclusionWe conclude that [¹⁸F]FDG is a more sensitive radiotracer than [^99mTc]MIBI for imaging of drug‐induced cardiomyopathy. We theorize that isoproterenol‐induced cardiomyopathy impacts cellular metabolism more than perfusion, which results in more substantial changes in [¹⁸F]FDG uptake than in [^99mTc]MIBI accumulation in cardiac tissue.     

Vascular Uptake on 18F-FDG PET/CT During the Clinically Inactive State of Takayasu Arteritis Is Associated with a Higher Risk of Relapse

PurposeTo evaluate whether vascular uptake on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) during the clinically inactive state of Takayasu arteritis (TAK) is associated with disease relapse.Materials and MethodsPatients with TAK who underwent ¹⁸F-FDG PET/CT during the clinically inactive state of the disease between 2006 and 2019 were included. Clinically inactive disease was defined as a status not fulfilling the National Institutes of Health (NIH) criteria for active disease in TAK. Relapse was defined as recurrence of clinically active disease after a clinically inactive period, requiring change in the treatment regimen. Vascular uptake on ¹⁸F-FDG PET/CT was assessed using target/background ratio (TBR), calculated as arterial maximum standardized uptake value (SUV)/mean SUV in venous blood pool. Multivariable Cox regression analysis was performed to identify factors associated with relapse.ResultsA total of 33 patients with clinically inactive TAK were included. During a median observation period of 4.5 (0.9–8.1) years, relapse occurred in 9 (27.3%) patients at median 1.3 (0.7–6.9) years. Notably, TBR [1.5 (1.3–1.8) vs. 1.3 (1.1–1.4), p=0.044] was significantly higher in patients who relapsed than in those who did not. On multivariable Cox regression analysis, the presence of NIH criterion 2 [adjusted hazard ratio (HR): 7.044 (1.424–34.855), p=0.017] and TBR [adjusted HR: 11.533 (1.053–126.282), p=0.045] were significantly associated with an increased risk of relapse.ConclusionVascular uptake on ¹⁸F-FDG PET/CT and the presence of NIH criterion 2 are associated with future relapse in patients with clinically inactive TAK.     

Function of the shoulder muscles during arm elevation: an assessment using positron emission tomography

Although 2‐deoxy‐2‐[¹⁸F]fluoro‐D‐glucose (FDG) positron emission tomography (PET) has been used for the assessment of skeletal muscle activities, its application to the shoulder muscles is only sparse. The purpose of this study was to investigate the activities of the shoulder muscles during arm elevation using PET. Six healthy volunteers performed an arm elevation exercise before and after FDG injection. The exercise consisted of 200 repetitions of arm elevation in the scapular plane with a 0.25‐kg weight fixed to the wrist on both arms. PET examination was performed 50 min after FDG injection. For control data, PET scan was repeated for each subject on a separate day without any exercise. The volume of interest was established for each shoulder muscle. The subscapularis was divided into three portions (superior, middle, and inferior). The standardized uptake value (SUV) was calculated in each muscle to quantify its activity. The SUVs increased significantly after exercise in the deltoid, supraspinatus, and the superior portion of subscapularis. Among three divided portions of the subscapularis, the SUV of the superior one‐third was significantly greater than the rest of the muscle after exercise. Our current study clearly indicated that there were two functionally different portions in the subscapularis muscle and the superior one‐third played an important role during arm elevation in the scapular plane.     

Role of NMDA receptors in the increase of glucose metabolism in the rat brain induced by fluorocitrate

The effect of inhibition of glial metabolism by infusion of fluorocitrate (FC, 1 nmol/μl, 2 μl) into the right striatum of the rat brain on the glucose metabolism was studied. Significant increases in [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake (45 min) in the right cerebral cortex and striatum were observed 4 h after the infusion of FC, both as determined by the tissue dissection method and autoradiography. No significant increase in the initial uptake of [¹⁸F]FDG (1 min) was seen in the striatum. Pretreatment with dizocilpine (MK-801), an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced [¹⁸F]FDG uptake in not only FC infused hemisphere but also in the contralateral hemisphere (saline-infused side). The radioactivity concentrations in plasma at 1, 5 and 45 min after the [¹⁸F]FDG injection were not altered by MK-801. This effect of MK-801 on glucose metabolism observed in the rat brain infused with FC was different from previous reports which indicated an increase in glucose metabolism in some areas of normal rat brain. In addition, the enhancement of glucose metabolism in the striatum induced by FC was almost completely abolished by pretreatment with MK-801. In the cerebral cortex, the relative ratio of radioactivity concentration in the right hemisphere to that in the left hemisphere still remained 1.37 (tissue dissection method) or 1.55 (autoradiography), which indicated that MK-801 partially blocked the effect of FC of enhancing glucose metabolism in this region. These results indicate an important role of NMDA-mediated signal transmission on the increase of glucose utilization induced by inhibition of glial metabolism.     

Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections

Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake may be observed in the course of active invasive fungal infections. The aim of this study was to assess the role of positron emission tomography with [¹⁸F]FDG ([¹⁸F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [¹⁸F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6–75 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplantation (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidiasis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomycosis in one case each. An increased uptake of [¹⁸F]FDG was observed in all areas previously identified by computed tomography and/or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [¹⁸F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [¹⁸F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [¹⁸F]FDG-PET was performed to assess the evolution of the disease. [¹⁸F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [¹⁸F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.     

Preclinical evaluation of 2-[18F]fluorodeoxysorbitol as a tracer for targeted imaging of Enterobacterales infection

Fluorine-18-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (¹⁸F-FDG-PET) is widely used for the detection of inflammatory and infectious diseases. Although this modality has proven to be a useful diagnostic tool, reliable distinction of bacterial infection from sterile inflammation or even from a malignancy remains challenging. Therefore, there is a need for bacteria-specific tracers for PET imaging that facilitate a reliable distinction of bacterial infection from other pathology. The present study was aimed at exploring the potential of 2-[¹⁸F]-fluorodeoxysorbitol ([¹⁸F]FDS) as a tracer for detection of Enterobacterales infections. Sorbitol is a sugar alcohol that is commonly metabolized by bacteria of the Enterobacterales order, but not by mammalian cells, which makes it an attractive candidate for targeted bacterial imaging. The latter is important in view of the serious clinical implications of infections caused by Enterobacterales. Here we demonstrate that sorbitol-based PET can be applied to detect a broad range of clinical bacterial isolates not only in vitro, but also in blood and ascites samples from patients suffering from Enterobacterales infections. Notably, the possible application of [¹⁸F]FDS is not limited to Enterobacterales since Pseudomonas aeruginosa and Corynebacterium jeikeium also showed substantial uptake of this tracer. We conclude that [¹⁸F]FDS is a promising tracer for PET-imaging of infections caused by a group of bacteria that can cause serious invasive disease.     

In vivo characterization of metabotropic glutamate receptor type 5 abnormalities in behavioral variant FTD

Although the pathogenesis underlying behavioral variant frontotemporal dementia (bvFTD) has yet to be fully understood, glutamatergic abnormalities have been hypothesized to play an important role. The aim of the present study was to determine the availability of the metabotropic glutamate receptor type 5 (mGluR5) using a novel positron emission tomography (PET) radiopharmaceutical with high selectivity for mGluR5 ([¹¹C]ABP688) in a sample of bvFTD patients. In addition, we sought to determine the overlap between availability of mGluR5 and neurodegeneration, as measured using [¹⁸F]FDG-PET and voxel-based morphometry (VBM). Availability of mGluR5 and glucose metabolism ([¹⁸F]FDG) were measured in bvFTD (n = 5) and cognitively normal (CN) subjects (n = 10). [¹¹C]ABP688 binding potential maps (BP_ND) were calculated using the cerebellum as a reference region, with [¹⁸F]FDG standardized uptake ratio maps (SUV_R) normalized to the pons. Grey matter (GM) concentrations were determined using VBM. Voxel-based group differences were obtained using RMINC. BvFTD patients showed widespread decrements in [¹¹C]ABP688 BP_ND throughout frontal, temporal and subcortical areas. These areas were likewise characterized by significant hypometabolism and GM loss, with overlap between reduced [¹¹C]ABP688 BP_ND and hypometabolism superior to that for GM atrophy. Several regions were characterized only by decreased binding of [¹¹C]ABP688. The present findings represent the first in vivo report of decreased availability of mGluR5 in bvFTD. This study suggests that glutamate excitotoxicity may play a role in the pathogenesis of bvFTD and that [¹¹C]ABP688 may prove a suitable marker of glutamatergic neurotransmission in vivo.     

Cognition, glucose metabolism and amyloid burden in Alzheimer's disease

The authors investigated relationships between glucose metabolism, amyloid load, and measures of cognitive and functional impairment in Alzheimer's disease (AD). Patients meeting criteria for probable AD underwent ¹¹C-labeled Pittsburgh Compound-B ([¹¹C]PIB) and 18F-fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) imaging and were assessed on a set of clinical measures. The Pittsburgh Compound-B (PIB) Distribution volume ratios and fluorodeoxyglucose (FDG) scans were spatially normalized and average PIB counts from regions-of-interest (ROI) were used to compute a measure of global PIB uptake. Separate voxel-wise regressions explored local and global relationships between metabolism, amyloid burden, and clinical measures. Regressions reflected cognitive domains assessed by individual measures, with visuospatial tests associated with more posterior metabolism, and language tests associated with metabolism in the left hemisphere. Correlating regional FDG uptake with these measures confirmed these findings. In contrast, no correlations were found between either voxel-wise or regional PIB uptake and any of the clinical measures. Finally, there were no associations between regional PIB and FDG uptake. We conclude that regional and global amyloid burden does not correlate with clinical status or glucose metabolism in AD.     

In‐vivo quantitative assessment of the therapeutic response in a mouse model of collagen‐induced arthritis using 18F‐fluorodeoxyglucose positron emission tomography

Mouse collagen‐induced arthritis (CIA) is the most commonly used animal model to investigate underlying pathogenesis of autoimmune arthritis and to demonstrate the therapeutic efficacy of novel drugs in autoimmune arthritis. The conventional read‐outs of CIA are clinical score and histopathology, which have several limitations, including (i) subjected to observer bias; and (ii) longitudinal therapeutic efficacy of a new drug cannot be determined. Thus, a robust, non‐invasive, in‐vivo drug screening tool is currently an unmet need. Here we have assessed the utility of ¹⁸F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG) as an in‐vivo screening tool for anti‐inflammatory drugs using the mouse CIA model. The radiotracer ¹⁸F‐FDG and a PET scanner were employed to monitor CIA disease activity before and after murine anti‐tumour necrosis factor (TNF)‐α antibody (CNTO5048) therapy in the mouse CIA model. Radiotracer concentration was derived from PET images for individual limb joints and on a per‐limb basis, and Spearman's correlation coefficient (ρ) was determined with clinical score and histology of the affected limbs. CNTO5048 improved arthritis efficiently, as evidenced by clinical score and histopathology. PET showed an increased uptake of ¹⁸F‐FDG with the progression of the disease and a significant decrease in the post‐treatment group. ¹⁸F‐FDG uptake patterns showed a strong correlation with clinical score (ρ = 0·71, P < 0·05) and histopathology (ρ = 0·76, P < 0·05). This study demonstrates the potential of ¹⁸F‐FDG PET as a tool for in‐vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.     

Para-chloro-2-[18F]fluoroethyl-etomidate: A promising new PET radiotracer for adrenocortical imaging

Introduction: [¹¹C]Metomidate ([¹¹C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [¹¹C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting.Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T_1/2=109.5 min) etomidate analogue, para-chloro-2-[¹⁸F]fluoroethyl etomidate; [¹⁸F]CETO, as an adrenal PET tracer.Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [¹⁸F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [¹¹C]MTO.Results: The binding of [¹⁸F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro K_d of 0.66 nM. Non-specific uptake of [¹⁸F]CETO in NHP liver was found to be low compared to that of [¹¹C]MTO.Conclusions: High specificity of [¹⁸F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [¹¹C]MTO. Non-specific binding to the liver was significantly lower than that of [¹¹C]MTO. [¹⁸F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.     

Role of lactate in the brain energy metabolism: revealed by Bioradiography

To elucidate the role of lactate in the brain, we used a novel method, 'Bioradiography', in which the dynamic process could be followed in living slices by use of positron-emitter-labeled compounds and imaging plates. We studied the incorporation of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) into rat brain slices incubated in oxygenated Krebs-Ringer solution. Under the glucose-free condition, [18F]FDG uptake rate in the cerebral cortex decreased with time and plateaued within 350 min but the addition of 5 mM lactate made the [18F]FDG uptake linear. When an inhibitor of the lactate transporter, 0.5 mM alpha-cyano-4-hydroxycinnamate (4-CIN) was applied to the glucose-free solution, the uptake rate decreased. Under the normal glucose condition, [18F]FDG uptake linearly increased for 6 h, but when 10 mM lactate was applied, the uptake rate decreased. In contrast, when 0.5 mM 4-CIN was applied to the normal glucose solution, [18F]FDG uptake rate increased. These results suggest that exogenous and endogenous lactate can substitute for glucose in the brain.     

In vivo evaluation of amyloid deposition and brain glucose metabolism of 5XFAD mice using positron emission tomography

Positron emission tomography (PET) has been used extensively to evaluate the neuropathology of Alzheimer's disease (AD) in vivo. Radiotracers directed toward the amyloid deposition such as [¹⁸F]-FDDNP (2-(1-{6-[(2-[F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) and [¹¹C]-PIB (Pittsburg compound B) have shown exceptional value in animal models and AD patients. Previously, the glucose analogue [¹⁸F]-FDG (2-[(18)F]fluorodeoxyglucose) allowed researchers and clinicians to evaluate the brain glucose consumption and proved its utility for the early diagnosis and the monitoring of the progression of AD. Animal models of AD are based on the transgenic expression of different human mutant genes linked to familial AD. The novel transgenic 5XFAD mouse containing 5 mutated genes in its genome has been proposed as an AD model with rapid and massive cerebral amyloid deposition. PET studies performed with animal-dedicated scanners indicate that PET with amyloid-targeted radiotracers can detect the pathological amyloid deposition in transgenic mice and rats. However, in other studies no differences were found between transgenic mice and their wild type littermates. We sought to investigate in 5XFAD mice if the radiotracers [¹¹C]-PIB, and [¹⁸F]-Florbetapir could quantify the amyloid deposition in vivo and if [¹⁸F]-FDG could do so with regard to glucose consumption. We found that 5XFAD animals presented higher cerebral binding of [¹⁸F]-Florbetapir, [¹¹C]-PIB, and [¹⁸F]-FDG. These results support the use of amyloid PET radiotracers for the evaluation of AD animal models. Probably, the increased uptake observed with [¹⁸F]-FDG is a consequence of glial activation that occurs in 5XFAD mice.     

Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study

Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre‐therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high‐grade glioma, where we directly compared the two currently most promising techniques, namely the MR‐based relative oxygen extraction fraction (MR‐rOEF) and the PET hypoxia marker H‐1‐(3‐[¹⁸F]‐fluoro‐2‐hydroxypropyl)‐2‐nitroimidazole ([¹⁸F]‐FMISO). MR‐rOEF was determined from separate measurements of T₂, T₂* and relative cerebral blood volume (rCBV) employing a multi‐parametric approach for quantification of the blood‐oxygenation‐level‐dependent (BOLD) effect. With respect to [¹⁸F]‐FMISO‐PET, besides the commonly used late uptake between 120 and 130 min ([¹⁸F]‐FMISO_{120–130 min}), we also analyzed the hypoxia specific uptake rate [¹⁸F]‐FMISO‐k₃, as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [¹⁸F]‐FMISO data was sensitive to a low signal‐to‐noise‐ratio, analysis was restricted to high‐uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia‐related parameter maps revealed that high MR‐rOEF values clustered in (edematous) peritumoral tissue, while areas with high [¹⁸F]‐FMISO_{120–130 min} concentrated in and around active tumor with disrupted blood–brain barrier, i.e. contrast enhancement in T₁‐weighted MRI. Volume‐of‐interest‐based correlations between MR‐rOEF and [¹⁸F]‐FMISO_{120–130 min} as well as [¹⁸F]‐FMISO‐k₃, and voxel‐wise analyses in individual patients, yielded limited correlations, supporting the notion that [¹⁸F]‐FMISO uptake, even after 2 h, might still be influenced by perfusion while [¹⁸F]‐FMISO‐k₃ was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR‐rOEF, and severe tissue hypoxia, as measured by [¹⁸F]‐FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high‐grade glioma biology.     

Simultaneous imaging of hyperpolarized [1,4‐13C2]fumarate, [1‐13C]pyruvate and 18F–FDG in a rat model of necrosis in a clinical PET/MR scanner

A co‐polarization scheme for [1,4‐¹³C₂]fumarate and [1‐¹³C]pyruvate is presented to simultaneously assess necrosis and metabolism in rats with hyperpolarized ¹³C magnetic resonance (MR). The co‐polarization was performed in a SPINlab polarizer. In addition, the feasibility of simultaneous positron emission tomography (PET) and MR of small animals with a clinical PET/MR scanner is demonstrated. The hyperpolarized metabolic MR and PET was demonstrated in a rat model of necrosis. The polarization and T₁ of the co‐polarized [1,4‐¹³C₂]fumarate and [1‐¹³C]pyruvate substrates were measured in vitro and compared with those obtained when the substrates were polarized individually. A polarization of 36 ± 4% for fumarate and 37 ± 6% for pyruvate was obtained. We found no significant difference in the polarization and T₁ values between the dual and single substrate polarization. Rats weighing about 400 g were injected intramuscularly in one of the hind legs with 200 μL of turpentine to induce necrosis. Two hours later, ¹³C metabolic maps were obtained with a chemical shift imaging sequence (16 × 16) with a resolution of 3.1 × 5.0 × 25.0 mm³. The ¹³C spectroscopic images were acquired in 12 s, followed by an 8‐min ¹⁸F‐2‐fluoro‐2‐deoxy‐d ‐glucose (¹⁸F–FDG) PET acquisition with a resolution of 3.5 mm. [1,4‐¹³C₂]Malate was observed from the tissue injected with turpentine indicating necrosis. Normal [1‐¹³C]pyruvate metabolism and ¹⁸F–FDG uptake were observed from the same tissue. The proposed co‐polarization scheme provides a means to utilize multiple imaging agents simultaneously, and thus to probe various metabolic pathways in a single examination. Moreover, it demonstrates the feasibility of small animal research on a clinical PET/MR scanner for combined PET and hyperpolarized metabolic MR.     

Evaluation of Semiautomatic and Deep Learning–Based Fully Automatic Segmentation Methods on [18F]FDG PET/CT Images from Patients with Lymphoma: Influence on Tumor Characterization

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [¹⁸F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [¹⁸F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k-means and Bayesian clustering, and a self-adaptive configuration (SAC) of k-means and Bayesian was applied. Three state-of-the-art deep learning–based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [¹⁸F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers’ DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning–based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning–based segmentation can achieve overall good segmentation results but failed in few patients impacting patients’ clinical evaluation.

     

Determination of muscular fatigue in elite runners

This study analyses the changes in the electromyographic activity (EMG) of six major muscles of the leg during an incremental running test carried out on a treadmill. These muscles, the gluteus maximus (GM), biceps femoris (BF), vastus lateralis (VL), rectus femoris (RF), tibialis anterior (TA) and gastrocnemius (Ga) are known to have quite different functions during running. The aim of this study was to develop a methodology adapted to the analysis of integrated EMG (iEMG) running results, and to test the chronology of the onset of fatigue of the major muscles involved in running. Nine well-trained subjects [ O_2max 76 (2.9) ml.min^–1.kg^–1] took part in this study. They completed a running protocol consisting of 4 min stages, incrementally increasing in speed until exhaustion. The EMG signal was recorded during ten bursts of activation analysed separately at 45 s and 3 min 40 s of each stage. During running, consideration of the alteration in stride frequency with either an increase in speed or the onset of fatigue appears to be an indispensable part of the assessment of muscular fatigue. This allows the comparison of muscular activation between the various stage speeds by the use of common working units. Distance seems to be the only working unit that allows this comparison and thus the determination of the appearance of fatigue during running. The biarticular hip-mobilising muscles (RF and BF), which present two different bursts of activation during one running cycle, are the muscles that show the earliest signs of fatigue.     

Correlation of PET/CT Standardized Uptake Value Measurements Between Dedicated Workstations and a PACS-Integrated Workstation System

Purpose This study was conducted to evaluate the clinical utility of a Positron Emission Tomography/Computed Tomography (PET/CT) analysis module of a picture archiving communication system (PACS) workstation in comparison to a dedicated PET/CT interpretation workstation. Materials and Methods The study included 32 consecutive patients referred for an [¹⁸F] Fluro-2-Deoxy-D-Glucose (¹⁸F-FDG) PET/CT at our institution. Images were reviewed at dedicated PET/CT and at PACS-integrated workstations. Mean standardized uptake values (SUVs) were calculated for the liver and the lung. Maximum SUVs were recorded for the bladder and an index lesion with the highest FDG uptake. The time spent for SUV measurements was recorded. Correlation of the SUV measurements was calculated with the Pearson coefficient. Results Pearson coefficients between the workstations ranged from 0.96 to 0.99 for bladder and lesion maximum SUVs. For liver and lung average SUVs, the coefficients varied from 0.53 to 0.98. The mean time spent to perform the four SUV measurements was 122.6 s for the dedicated workstations and 134.6 s for the PACS-integrated system. Conclusion The correlation of SUV measurements between dedicated PET/CT and PACS-integrated workstations is very good, especially for maximum SUVs. For routine reading of PET/CT scans, a PACS workstation with a PET/CT analysis module offers an excellent alternative to the use of a dedicated PET/CT workstation.     

18F-FDG Positron-Emission Tomography/Computed Tomography Findings of Radiographic Lesions Suggesting Old Healed Tuberculosis

The presence of radiographic lesions suggesting old healed tuberculosis (TB) is one of the strongest risk factors for the subsequent development of active TB. We elucidated the metabolic activity of radiographic lesions suggesting old healed TB using ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT). This cross-sectional study included 63 participants with radiographic lesions suggesting old healed TB and with available ¹⁸F-FDG PET/CT scans. The maximum standardized uptake value (SUV_max) measured in the lesions, the clinical characteristics, results of the tuberculin skin test (TST) and interferon-γ release assay (IGRA) were analyzed. The SUV_max in old healed TB was 1.5 or higher among nine (14.3%) participants. Age (adjusted odds ratio [aOR], 1.23; 95% CI, 1.03-1.46), history of previous TB (aOR, 60.43; 95% CI, 1.71-2131.65), and extent of the lesions (aOR, 1.34; 95% CI, 1.02-1.75) were associated with higher SUV_max. The positive rates for the TST and IGRA were not different between groups with and without increased FDG uptake. Increased FDG uptake on ¹⁸F-FDG PET/CT was observed in a subset of patients with radiographic lesions suggesting old healed TB. Given that the factors associated with increased FDG uptake are known risk factors for TB development, the possibility exists that participants with old healed TB lesions with higher SUV on ¹⁸F-FDG PET/CT scans might be at higher risk for active TB.

Graphical Abstract

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