Repeatability of [15O]H2O PET imaging for lower extremity skeletal muscle perfusion: a test-retest study.

BACKGROUND: [15O]H2O PET/CT allows noninvasive quantification of tissue perfusion and can potentially play a future role in the diagnosis and treatment of peripheral artery disease. We aimed to evaluate the reliability of dynamic [15O]H2O PET imaging for measuring lower extremity skeletal muscle perfusion. Ten healthy participants underwent same-day test-retest study with six dynamic [15O]H2O PET scans of lower legs and feet. Manual volume-of-interests were drawn in skeletal muscles, and PET time activity curves were extracted. K1 values (mL/min/100 mL) were estimated using a single-tissue compartment model (1TCM), autoradiography (ARG), and parametric imaging with blood input functions obtained from separate heart scans. RESULTS: Resting perfusion values in the muscle groups of the lower legs ranged from 1.18 to 5.38 mL/min/100 mL (ARG method). In the muscle groups of the feet, perfusion values ranged from 0.41 to 3.41 mL/min/100 mL (ARG method). Test-retest scans demonstrated a strong correlation and good repeatability for skeletal muscle perfusion with an intraclass correlation coefficient (ICC) of 0.88 and 0.87 and a repeatability coefficient of 34% and 53% for lower legs and feet, respectively. An excellent correlation was demonstrated when comparing volume-of-interest-based methods (1TCM and ARG) (lower legs: ICC = 0.96, feet: ICC = 0.99). Parametric images were in excellent agreement with the volume-of-interest-based ARG method (lower legs: ICC = 0.97, feet: ICC = 0.98). CONCLUSION: Parametric images and volume-of-interest-based methods demonstrated comparable resting perfusion values in the lower legs and feet of healthy individuals. The largest variation was seen between individuals, whereas a smaller variation was seen between muscle groups. Repeated measurements of resting blood flow yielded a strong overall correlation for all methods.

Whole-Body and Forearm Muscle Protein Metabolism in Patients With Acromegaly Before and After Treatment.

BACKGROUND: Active acromegaly is characterized by increased lean body mass, but the mechanisms underlying the protein anabolic effect are unclear. AIM: To study if active acromegaly induces reversible changes in whole-body and skeletal muscle protein kinetics. PATIENTS AND METHODS: Eighteen patients with acromegaly were investigated before and 47 ± 10 weeks after disease control by surgery (n = 8) and/or medical treatment (n = 10). Labeled phenylalanine and tyrosine tracers were employed to assess whole-body and regional forearm muscle protein kinetics. Intramyocellular protein signaling was assessed in skeletal muscle biopsies, and whole-body dual-energy X-ray absorptiometry scan and indirect calorimetry assessed lean body mass (LBM) and resting energy expenditure, respectively. RESULTS: Disease control induced a 7% decrease in lean body mass (P < .000) and a 14% decrease in LBM-adjusted energy expenditure. Whole-body phenylalanine breakdown decreased after disease control (P = .005) accompanied by a decrease in the degradation of phenylalanine to tyrosine (P = .005) and a decrease in whole-body phenylalanine synthesis (P = .030). Skeletal muscle protein synthesis tended to decrease after disease control (P = .122), whereas the muscle protein breakdown (P = .437) and muscle protein loss were unaltered (P = .371). Unc-51 like autophagy activating kinase 1 phosphorylation, an activator of protein breakdown, increased after disease control (P = .042). CONCLUSIONS: Active acromegaly represents a reversible high flux state in which both whole-body protein breakdown and synthesis are increased, whereas forearm muscle protein kinetics are unaltered. Future studies are needed to decipher the link between protein kinetics and the structure and function of the associated growth hormone-induced increase in lean body mass.

Extracardiac findings with increased perfusion during clinical O-15-H2O PET/CT myocardial perfusion imaging: A case series.

BACKGROUND: Coincidental extracardiac findings with increased perfusion were reported during myocardial perfusion imaging (MPI) with various retention radiotracers. Clinical parametric O-15-H2O PET MPI yielding quantitative measures of myocardial blood flow (MBF) was recently implemented at our facility. We aim to explore whether similar extracardiac findings are observed using O-15-H2O. METHODS AND RESULTS: All patients (2963) were scanned with O-15-H2O PET MPI according to international guidelines and extracardiac findings were collected. In contrast to parametric O-15-H2O MBF images, extracardiac perfusion was assessed using summed images. Biopsy histopathology and other imaging modalities served as reference standards. Various malignant lesions with increased perfusion were detected, including lymphomas, large-celled neuroendocrine tumour, breast, and lung cancer plus metastases from colonic and renal cell carcinomas. Furthermore, inflammatory and hyperplastic benign conditions with increased perfusion were observed: rib fractures, gynecomastia, atelectasis, sarcoidosis, pneumonia, chronic lung inflammation and fibrosis, benign lung nodule, chronic diffuse lung infiltrates, pleural plaques and COVID-19 infiltrates. CONCLUSIONS: Malignant and benign extracardiac coincidental findings with increased perfusion are readily visible and frequently seen on O-15-H2O PET MPI. We recommend evaluating the summed O-15-H2O PET images in addition to the low-dose CT attenuation images.

Ectopic lipid deposition and insulin resistance in patients with GH disorders before and after treatment.

OBJECTIVES: Insulin resistance is associated with ectopic lipid deposition. Growth hormone (GH) status also modulates ectopic lipid accumulation, but how this associates with insulin resistance in patients with GH disorders is not well established. DESIGN AND METHODS: Twenty-one patients diagnosed with acromegaly and 12 patients with adult GH deficiency (GHD) were studied at diagnosis and after treatment. A reference group of 12 subjects was included. Each study day comprised assessment of body composition with dual-energy X-ray absorptiometry, ectopic lipid deposition in the liver by MR spectroscopy, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). RESULTS: Disease control of acromegaly decreased lean body mass (LBM) (P < .000) and increased the percentage of total body fat (TBF) (P < .000). GH replacement increased LBM in the GHD patients (P = .007) and decreased the percentage of TBF (P = .010). The intrahepatic lipid (IHL) content increased after disease control in acromegaly (P = .004), whereas IHL did not change significantly after GH replacement in GHD (P = .34). Insulin resistance (HOMA-IR) improved after disease control of acromegaly (P < .000) and remained unaltered after GH replacement in the GHD patients (P = .829). CONCLUSIONS: GH status is a significant modulator of body composition and insulin sensitivity.GH excess reduces total fat mass and intrahepatic lipid content together with induction of insulin resistance.The data support the notion that GH-induced insulin resistance is unassociated with hepatic lipid accumulation.

Skeletal "Superscan" With 11 C-Methionine PET/CT in Polycythemia Vera.

ABSTRACT: 11 C-methionine PET/CT for parathyroid adenoma localization on a 60-year-old woman known with polycythemia vera revealed highly methionine-avid red bone marrow, an uptake pattern that has previously been described in hematological disease such as multiple myeloma. An equivalent skeletal "superscan" pattern in polycythemia vera has been described with other PET tracers, but this case illustrates that this pattern can be seen with 11 C-methionine PET/CT as well and can be added to the list of potential pitfalls.

A Persistent Left-Sided Superior Vena Cava Detected on a O-15-H 2 O PET/CT of the Heart.

ABSTRACT: A persistent left-sided superior vena cava (PLSVC) is an uncommon finding with a prevalence of up to 0.5% in the general population. The PLSVC appears when the left anterior cardinal vein fails to regress as the ligament of Marshall during embryologic development. It is usually asymptomatic and discovered incidentally; however, its recognition is important because it might complicate invasive cardiovascular procedures. In this case, we report an incidental finding of a PLSVC detected on the O-15-H 2 O PET/CT of a patient who was referred for myocardial perfusion imaging.

Reversible insulin resistance in muscle and fat unrelated to the metabolic syndrome in patients with acromegaly.

BACKGROUND: Patients with active acromegaly exhibit insulin resistance despite a lean phenotype whereas controlled disease improves insulin sensitivity and increases fat mass. The mechanisms underlying this paradox remain elusive, but growth hormone (GH)-induced lipolysis plays a central role. The aim of the study was to investigative the molecular mechanisms of insulin resistance dissociated from obesity in patients with acromegaly. METHODS: In a prospective study, twenty-one patients with newly diagnosed acromegaly were studied at diagnosis and after disease control obtained by either surgery alone (n=10) or somatostatin analogue (SA) treatment (n=11) with assessment of body composition (DXA scan), whole body and tissue-specific insulin sensitivity and GH and insulin signalling in adipose tissue and skeletal muscle. FINDINGS: Disease control of acromegaly significantly reduced lean body mass (p<0.001) and increased fat mass (p<0.001). At diagnosis, GH signalling (pSTAT5) was constitutively activated in fat and enhanced expression of GH-regulated genes (CISH and IGF-I) were detected in muscle and fat. Insulin sensitivity in skeletal muscle, liver and adipose tissue increased after disease control regardless of treatment modality. This was associated with enhanced insulin signalling in both muscle and fat including downregulation of phosphatase and tensin homolog (PTEN) together with reduced signalling of GH and lipolytic activators in fat. INTERPRETATION: In conclusion, the study support that uncontrolled lipolysis is a major feature of insulin resistance in active acromegaly, and is characterized by upregulation of PTEN and suppression of insulin signalling in both muscle and fat. FUNDING: This work was supported by a grant from the Independent Research Fund, Denmark (7016-00303A) and from the Alfred Benzon Foundation, Denmark.

Lumbar Osteophyte Avid on 68Ga-Prostate-Specific Membrane Antigen PET/CT.

A 75-year-old man with recently diagnosed high-risk prostate cancer was referred for primary staging with Ga-prostate-specific membrane antigen (PSMA) PET/CT. The scan revealed intense Ga-PSMA uptake in a lumbar osteophyte on the right side of level L2/L3, whereas several other spinal osteophytes showed no Ga-PSMA uptake. MRI findings in the L3 vertebra was consistent with a benign Modic type 1 lesion, but MRI showed no signs of malignancy in the osteophyte with high Ga-PMSA uptake. This case presents an osteophyte as an addition to the list of potential benign pitfalls to be aware of when interpreting Ga-PSMA PET/CT.