High FDG Uptake Research Articles

FDG PET/CT and Enhanced CT Imaging of Tumor Heterogeneity in Hepatocellular Carcinoma

Tumor heterogeneity is used to define the appearance of different histological differentiation within a single neoplasm. We present a case of single hepatocellular carcinoma showing both low and high FDG uptake areas. The low FDG uptake area was corresponding to low-grade HCC, and the high FDG uptake area was corresponding to high-grade HCC. This case indicates that the tumor grades affect intratumoral heterogeneity in FDG distribution. FDG PET/CT can be useful for guiding tissue sampling of the HCC with heterogeneous histological differentiations, and obviating overestimation or underestimation of the proportion of the higher-risk cell population.

Evaluation of physiological FDG uptake in the skeleton in adults: Is it uniformly distributed?

AimThe aim of this study was to study whether FDG was uniformly distributed throughout the skeleton and whether age and gender affected this biodistribution. Material and MethodsA total of 158 patients were included in this retrospective study. None of the patients had received prior treatment that had affected the bone marrow and patients with bone metastases, trauma, benign and/or malignant hematologic disorders were excluded from the study. The SUVmax from the 24 different locations in the skeleton was obtained and all the values were compared with each other. ResultsFDG uptake in the skeleton was not uniform in both sexes. While the highest FDG uptake was seen in the L3 vertebra, the lowest glucose metabolism was observed in the diaphysis of the femur. Concerning the vertebral column, FDG uptakes were also non-uniform and the SUVmax gradually increased from the cervix to the lumbar spine. The mean skeletal SUVmax was decreased in accordance with age in both genders. ConclusionFDG was not uniformly distributed throughout the skeleton in both sexes. It had a tendency to increase from the appendicular to axial skeleton and from cervical to lumbar spine in the vertebral column that may be related with the normal distribution of the red bone marrow. Additionally, the glycolytic metabolism of the whole skeleton was gradually decreased in accordance with the age in both sexes.

Study of prognostic prediction using pre-treatment PET/CT in oral cancer patients

We performed a clinico-statistical study of patients with oral cancer that were taken positron emission tomography combined with computed tomography (PET/CT) as preoperative examination in the past eight years at our department. The aim of this retrospective study was to investigate relevance of prognosis and pre-treatment [18F]-2-fluorodeoxyglucose (18F-FDG) uptake of the primary tumor, assessed by PET/CT in oral cancer patients of our department. There has been already reported that high FDG uptake is clinically correlated with shorter survival, lymph node metastasis, and poor response to such therapies as surgery and radiotherapy. We investigated whether maximum standardized uptake value (SUVmax) of primary site assessed by 18F-FDG-PET/CT is correlated with overall survival in patient with oral squamous cell carcinoma.

FDG PET/CT in Peripheral Primitive Neuroectodermal Tumor of the Retroperitoneum

Peripheral primitive neuroectodermal tumor (pPNET) is a very aggressive neoplasm that predominantly affects children and adolescents with a poor prognosis. A 35-year-old woman presented with right upper abdominal pain for 2 weeks. Abdominal enhanced CT showed a large cystic-solid tumor in the left retroperitoneum, with progressive enhanced papillary projections of the wall. FDG PET/CT showed strong FDG uptake of the cystic wall with SUVmax of 17.2. The patient underwent completed resection of the tumor. pPNET was confirmed by pathology. The high FDG uptake of the tumor may be related to its high proliferative index revealed by Ki-67.

Geometric distortions of diffusion weighted imaging of the head/neck in combined PET/MR: optimization of image acquisition and post-processing correction for oncology applications.

The combination of PET with Diffusion Weighted Imaging (DWI) is a promising application of PET/MR. DWI geometric accuracy can be compromised in body regions with complex anatomy. Here, we assess DWI head/neck image quality following optimization of acquisition and post-processing. Preliminary data from 10 patients with cancer of the tonsil or base-of-tongue is presented. An integrated PET/MR system (Siemens Biograph mMR) with a 3 T magnet was used. PET was performed as a single-bed, 20 min acquisition, 120 min post injection of 4 MBq/kg [18F]-FDG. MRI included axial T2 weighted STIR, B0 mapping and 2 DWI single-shot EPI measurements (DWI1 and DWI2) with b values 0, 500 and 1000 mm2/s. DWI2 was measured as 3 stacks, each at isocenter to maximize field homogeneity. DWI1/DWI2 had an effective echo spacing 0.375/0.145 ms. For DWI2, distortions were corrected using FSL with FUGUE and Topup algorithms. DWI geometric quality was evaluated in 44×44 mm2 region centred on the tumor, with the STIR image as anatomical reference. Correlation and DICE coefficients between DWI b0 and STIR images were computed, for all DWI image sets. Geometric quality of DWI1 was poor, but improved both by optimization of acquisition (DWI2) and by post-processing. Visually, hyperintensities on the Topup corrected DWI2 images matched closely the STIR images. Also, regions with high FDG uptake and low diffusion had matching shapes. Correlation and DICE coefficients had a large variation for DWI1, and showed an overall increase to a high level >0.6 and 0.8, respectively, following optimization of image acquisition and post-processing correction. Diffusion weighted images of the head/neck with a quality suitable for dual-modality assessment of tumour characteristics on a voxel basis can be obtained following the optimization of acquisition and post-processing.

Primary bone lymphoma: A case report and review of the literature.

Primary lymphoma of the bone (PLB) primarily arising from the medullary cavity is an extremely rare entity, with only retrospective studies and sporadic cases reported in the literature. The current study presents one case of PLB treated with chemotherapy and radiotherapy, and a review of the literature to elucidate the optimal treatment of PLB. A 73-year-old female presented with pain in the left hip that had persisted for two months. Plain X-ray and magnetic resonance imaging of the left hip showed lytic areas involving the left innominatum. Technetium-99m radionuclide imaging showed increased tracer uptake in the ilium, acetabulum and ischium. An 18F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) scan showed high FDG uptake. A fine-needle aspiration biopsy of the lesion was performed, and histopathological and immunohistochemical examination confirmed a diagnosis of B-cell lymphoma. The patient received radiation therapy followed by six cycles of CHOP regimen (1,000 mg cyclophosphamide, 80 mg epirubicine and 2 mg vincristine on day one, and 100 mg prednisone on days one to five, every three weeks) and achieved a complete response, as confirmed by FDG-PET-CT. At present, the patient is in a good condition. This case is noteworthy, as it is a well-documented case in which the patient received successful treatment. This case demonstrates that PLB has an improved prognosis compared with primary lymphoma of other sites; however, combined therapy may further improve the patient outcome.

Validation of nonrigid registration in pretreatment and follow-up PET/CT scans for quantification of tumor residue in lung cancer patients.

Nonrigid registrations of pre‐ and postradiotherapy (RT) PET/CT scans of NSCLC patients were performed with different algorithms and validated tracking internal landmarks. Dice overlap ratios (DR) of high FDG‐uptake areas in registered PET/CT scans were then calculated to study patterns of relapse. For 22 patients, pre‐ and post‐RT PET/CT scans were registered first rigidly and then nonrigidly. For three patients, two types (based on Demons or Morphons) of nonrigid registration algorithms each with four different parameter settings were applied and assessed using landmark validation. The two best performing methods were tested on all patients, who were then classified into three groups: large (Group 1), minor (Group 2) or insufficient improvement (Group 3) of registration accuracy. For Group 1 and 2, DRs between high FDG‐uptake areas in pre‐ and post‐RT PET scans were determined. Distances between corresponding landmarks on deformed pre‐RT and post‐RT scans decreased for all registration methods. Differences between Demons and Morphons methods were smaller than 1 mm. For Group 1, landmark distance decreased from 9.5 ± 2.1 mm to 3.8 ± 1.2 mm (mean ± 1 SD, p < 0.001), and for Group 3 from 13.6 ± 3.2 mm to 8.0 ± 2.2 mm (p=0.02). No significant change was observed for Group 2 where distances decreased from 5.6 ± 1.3 mm to 4.5 ± 1.1 mm (p=0.02). DRs of high FDG‐uptake areas improved significantly after nonrigid registration for most patients in Group 1. Landmark validation of nonrigid registration methods for follow‐up CT imaging in NSCLC is necessary. Nonrigid registration significantly improves matching between pre‐ and post‐RT CT scans for a subset of patients, although not in all patients. Hence, the quality of the registration needs to be assessed for each patient individually. Successful nonrigid registration increased the overlap between pre‐ and post‐RT high FDG‐uptake regions.PACS number: 87.57.Q‐, 87.57.C‐, 87.57.N‐, 87.57.‐s, 87.55.‐x, 87.55.D‐, 87.55.dh, 87.57.uk, 87.57.nj

Evaluation of physiological FDG uptake in the skeleton in adults: is it uniformly distributed?

The aim of this study was to study whether FDG was uniformly distributed throughout the skeleton and whether age and gender affected this biodistribution. A total of 158 patients were included in this retrospective study. None of the patients had received prior treatment that had affected the bone marrow and patients with bone metastases, trauma, benign and/or malignant hematologic disorders were excluded from the study. The SUVmax from the 24 different locations in the skeleton was obtained and all the values were compared with each other. FDG uptake in the skeleton was not uniform in both sexes. While the highest FDG uptake was seen in the L3 vertebra, the lowest glucose metabolism was observed in the diaphysis of the femur. Concerning the vertebral column, FDG uptakes were also non-uniform and the SUVmax gradually increased from the cervix to the lumbar spine. The mean skeletal SUVmax was decreased in accordance with age in both genders. FDG was not uniformly distributed throughout the skeleton in both sexes. It had a tendency to increase from the appendicular to axial skeleton and from cervical to lumbar spine in the vertebral column that may be related with the normal distribution of the red bone marrow. Additionally, the glycolytic metabolism of the whole skeleton was gradually decreased in accordance with the age in both sexes.

A case of rapidly progressing primary thyroid angiosarcoma in a Japanese man

Primary thyroid angiosarcoma is a very rare and aggressive disease, originally reported in patients from the Swiss Alpine region, but is rare in other parts of the world. We describe a Japanese case of primary angiosarcoma of the thyroid in a 64-year-old man, who presented with a rapidly enlarging painful neck mass. Fine-needle aspiration biopsy was performed, and the results were interpreted as malignant. FDG-PET-CT demonstrated a necrotic lesion on the right side of the neck with high FDG uptake. The patient underwent a total thyroidectomy. Pathological findings revealed a proliferation of atypical cells lined vascular spaces. Immunohistochemistry staining (IHCS) was positive for factor VIII, and CD31, but not CD34, and negative for CK 5, CK 7, and CK 20. From these findings, it was diagnosed as an epithelioid angiosarcoma. Two weeks after the operation, bilateral bloody pleural effusion was observed, and he died 3 months after the surgery.

Association between nonalcoholic fatty liver disease and carotid artery inflammation evaluated by 18F-fluorodeoxyglucose positron emission tomography.

We assessed the association between nonalcoholic fatty liver disease (NAFLD) and carotid artery inflammation measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. Participants were 755 consecutive otherwise healthy adult males who underwent a general health screening program. Carotid FDG uptake, represented as maximum target-to-background ratio, was increased with mild (n = 237; 1.61 ± 0.14; P = .033) and moderate NAFLD (n = 145; 1.63 ± 0.16; P = .005) compared with controls (n = 373; 1.58 ± 0.15). In patients aged >50 years, moderate NAFLD was the only independent risk factor for high carotid FDG uptake (odds ratio, 2.12; 95% confidence interval, 1.10-4.07; P = .001). Apparently healthy adult males with NAFLD have elevated carotid FDG uptake as well as increased carotid intima-media thickness, suggesting that they may be at an increased risk of having inflammatory atherosclerotic plaques in the carotid arteries.

Renaissance of (18)F-FDG positron emission tomography in the imaging of pheochromocytoma/paraganglioma.

Renaissance of (18)F-FDG positron emission tomography in the imaging of pheochromocytoma/paraganglioma.

Splenic lesion of IgG4-related disease in FDG-PET/CT

Recent several reports showed that 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scans accurately, and safely identifies the multiple organs’ involvements in IgG4-related diseases (IgG4-RD) patients. Disease activity in two patients, aged 74 and 73 years (serum IgG4, 807 and 1630 mg/dl, respectively), with IgG4-RD were monitored using FDG-PET/CT. Scans before treatment showed splenomegaly with high FDG uptake. Inflammatory aneurysm, submandibular gland swelling, splenomegaly and tubulointerstitial nephritis resolved after treatment with prednisolone. Follow-up FDG-PET/CT at 4 months, with no symptoms, showed a significant decrease in FDG accumulation and improvement of splenomegaly in splenic lesion of IgG4-RD. Thus, splenic lesions detected by FDG-PET/CT might be novel involvements of IgG4-RD.

FDG PET/CT in Malignant Eccrine Porocarcinoma Arising in a Pre-existing Poroma

In a 61-year-old man with known poroma of right lower abdomen, malignant transformation to porocarcinoma was suspected and confirmed by biopsy. PET/CT was requested for tumor staging, which revealed high FDG uptake in the known skin nodules located in the right side of abdominal and chest wall and identified further some adenopathy in the right axillary. All nodules and axillary lymph nodes were removed, and diagnosis of eccrine porocarcinoma was confirmed. The primary tumor and secondary lesions of porocarcinoma show a high glucose metabolism; thus, PET/CT could be useful for staging, follow-up, and detection of recurrence of patients with eccrine porocarcinoma.

Abstract 16: FDG-PET/CT Enables the Detection of Recurrent, Same-Site Deep Vein Thrombosis by Illuminating Recently Formed Neutrophil-Rich Thrombus

Background: Specific detection of recurrent deep vein thrombosis (DVT) is a challenging clinical problem. As DVT formation and resolution are inflammatory processes, we experimentally investigated whether noninvasive 18F-fluorodeoxyglucose (FDG)-PET imaging could identify inflamed, recently formed thrombi and thereby improve the diagnosis of recurrent DVT. Methods: We established a stasis-induced DVT model in murine jugular veins and also a novel model of recurrent stasis DVT in mice. C57BL/6 mice (n = 30) underwent ligation of the jugular vein to induce stasis DVT. FDG-PET/CT was performed at DVT timepoints of day 2, 4, 7, 14, or 2+16 (same-site recurrent day 2 DVT overlying a 16 days old DVT). Antibody-based neutrophil depletion was performed in a subset of mice prior to DVT formation and FDG-PET/CT. In a clinical study, 38 patients with lower extremity DVT or controls undergoing FDG-PET were retrospectively analyzed. Results: Stasis DVT demonstrated that the highest FDG signal occurred day 2, followed by a time-dependent decrease (p&lt;0.05). Histological analyses demonstrated that thrombus neutrophils (p&lt;0.01), but not macrophages, correlated with thrombus PET signal intensity. Neutrophil depletion decreased FDG signals in day 2 DVT compared to that of control mice (p&lt;0.05). Recurrent DVT demonstrated significantly higher FDG uptake than organized day 14 DVT (p&lt;0.05). The FDG DVT signal in patients also exhibited a time-dependent decrease (p&lt;0.05). Recurrent day 2 DVT showed neutrophil-dominant infiltration pattern with few macrophages, similar to standalone day 2 DVT. Conclusions: Noninvasive FDG-PET/CT identifies neutrophil-dependent thrombus inflammation in murine DVT, and demonstrates a time-dependent signal in both murine and clinical DVT. FDG-PET/CT may offer a molecular imaging strategy to accurately diagnose recurrent DVT.

Carotid Artery FDG Uptake May Serve as a Biomarker for Cardiovascular Risk Stratification in Asymptomatic Adults.

We investigated the relation between carotid artery FDG uptake and cardiovascular risk based on the Framingham risk score (FRS) and evaluated the possible role of FDG uptake in terms of risk stratification of asymptomatic adults. We evaluated 290 adults who underwent FDG PET/CT as part of general health screens. We calculated target-to-background ratios, corrected for pre-scan blood glucose levels, and obtained "TBRglu" values for both common carotid arteries. The FRS and the presence/absence of metabolic syndrome were recorded for each subject. Relationships among TBRglu values, metabolic syndrome status, and clinical parameters were assessed. Carotid artery FDG uptake was significantly associated with clinical risk factors. Stepwise multiple regression analysis revealed that triglyceride levels, diabetes, and metabolic syndrome were independent determinants of high TBRglu. Of subjects with metabolic syndrome, those exhibiting high carotid artery FDG uptake had significantly higher levels of high sensitivity C-reactive protein (hsCRP). In subjects who did not have metabolic syndrome, FRSs were significantly elevated in those exhibiting high carotid artery FDG uptake compared to those with low uptake (13.1 ± 7.0 vs. 8.2 ± 7.4), as was also true of subjects with the syndrome (21.8 ± 16.0 vs. 13.5 ± 11.9). High carotid FDG uptake is significantly associated with clinical risk factors and a greater FRS. Of subjects with metabolic syndrome, those with high carotid uptake had significantly higher hsCRP concentrations and FRSs. Therefore, carotid artery FDG activity may serve as a possible biomarker allowing cardiovascular risk stratification of asymptomatic populations.

Two patients with intestinal failure requiring home parenteral nutrition, a NOD2 mutation and tuberculous lymphadenitis

BackgroundMutations in the NOD2 gene are a significant risk factor to acquire intestinal failure requiring home parenteral nutrition. Tuberculous lymphadenitis is the main manifestation of extrapulmonary tuberculosis. Defects in the innate immunity, including NOD2 mutations, may increase the risk for acquiring infections caused by M. tuberculosis. An association of intestinal failure, mutations in the NOD2 gene and tuberculous lymphadenitis has not been described before.Case presentationWe report of two patients with intestinal failure secondary to mesenteric ischemia. Both patients presented with fever and weight loss while receiving long term home parenteral nutrition. Both of them were found to have mutations in the NOD2 gene. Catheter related infections were ruled out. FDG-PET-CT scans initially obtained in search for another infectious focus that would explain the symptoms unexpectedly showed high FDG uptake in mediastinal lymph nodes. Direct or indirect evidence proved or was highly suggestive for tuberculous lymphadenitis. Intravenous tuberculostatic therapy was started and led to a reversal of symptoms and to resolution of the lesions by FDG-PET-CT.ConclusionMutations in the NOD2 gene may put patients both at an increased risk for acquiring M. tuberculosis infections as well as at an increased risk of intestinal failure after extensive intestinal resection. Thus we suggest to specifically include reactivated and opportunistic infections in the differential diagnosis of suspected catheter related infection in patients with intestinal failure who carry mutations in their NOD2 gene.

Constant high adrenal FDG uptake in PET/CT associated with mitochondrial disease

We describe a patient with the m.3243A>G mitochondrial DNA mutation who developed sepsis caused by Streptococcus constellatus. In the acute phase of illness, abnormally high uptake of (18)F-FDG was observed in both adrenal glands that appeared anatomically normal. In repeated imaging six months later the adrenal uptake had diminished but remained clearly elevated. We did not observe high adrenal FDG uptake as in the patient described here among 30 patients with Staphylococcus aureus sepsis that were investigated with identical imaging protocol. In sepsis, oxygen consumption and metabolic rate are increased compared to normal metabolism. The observed high adrenal FDG uptake during sepsis in this patient probably reflects the acute metabolic stress induced by the infection. Interestingly, in repeated imaging six months later, the adrenal SUVs had diminished but were still abnormally high: this suggests constant high levels of metabolic stress associated with the mitochondrial disorder.

Inflammatory Myofibroblastic Tumor

The aim of this study was to evaluate retrospectively F-FDG PET/CT findings of inflammatory myofibroblastic tumor (IMT) and their correlation with the pathologic findings. FDG PET/CT findings were reviewed in 5 patients with IMT and 1 patient with spindle cell sarcoma transformed from IMT. PET/CT scans were performed in all 6 patients before surgery. Follow-up FDG PET/CT scan was performed in 1 patient. The location, size, maximal standardized uptake value (SUVmax), and pathologic findings of the tumors were reviewed. The correlation between the FDG uptake and pathologic findings were analyzed. A total of 10 lesions were detected in all 6 patients. The tumor locations were liver (n = 3), retroperitoneum (n = 2), spleen (n = 1), lung (n = 1), and bone (n = 3). Seven IMTs and 1 spindle cell sarcoma transformed from IMT were confirmed by pathology. The mean SUVmax of the pathologically proven tumors was 10.9 ± 5.5, with a high variability of SUVmax among tumors ranging from 3.3 to 20.8. The tumors (n = 7) with high cellularity had stronger FDG uptake, while the tumors (n = 1) with low cellularity had relatively low FDG uptake. The tumors with nuclear atypia and relatively high proliferative index had very strong FDG uptake, while those with low proliferative index or negative Ki-67 staining had relatively lower FDG uptake. One small tumor with abundant plasma cells showed high FDG uptake, while 1 large tumor with focal inflammatory cell infiltrate showed lower FDG uptake. One patient developed local recurrences and distant metastases revealed by the second FDG PET/CT scan 7 months after resection. FDG uptake in IMTs varied from low to high FDG uptake, which may be due to tumor cellularity, biological behaviors of the tumor cells, the composition and the proportion of inflammatory cells, and the extent of activation of the inflammatory cells. FDG PET/CT may be useful for detection of the primary tumors, local recurrences, and distant metastases.

An alternative approach to histopathological validation of PET imaging for radiation therapy image-guidance: A proof of concept

PurposeIn radiotherapy, PET images can be used to guide the delivery of selectively escalated doses to biologically relevant tumour subvolumes. Validation of PET for such applications requires demonstration of spatial coincidence between PET tracer uptake pattern and the histopathologically confirmed target. This study introduces a novel approach to histopathological validation of PET image segmentation for radiotherapy guidance. Methods and materialsSequential tissue sections from surgically excised whole-tumour specimens were used to acquire full 3D-sets of both histopathological images (microscopy) and PET tracer distribution images (autoradiography). After these datasets were accurately registered, a full 3D autoradiographic distribution of PET tracer was reconstructed and used to obtain synthetic PET images (sPET) by simulating the image deterioration induced by processes involved in PET image formation. To illustrate the method, sPET images were used in this study to investigate spatial coincidence between high FDG uptake areas and the distribution of viable tissue in two small animal tumour models. ResultsThe reconstructed 3D autoradiographic distribution of the PET tracer was spatially coherent, as indicated by the high average value of the normalised pixel-by-pixel correlation of intensities between successive slices (0.84±0.05 and 0.94±0.02). The loss of detail in the sPET images versus the 3D autoradiography was significant as indicated by Dice coefficient values corresponding to the two tumours (0 and 0.1 at 70% threshold). The maximum overlap between the FDG segmented volumes and the extent of the viable tissue as indicated by Dice coefficient values, was 0.8 for one tumour (for the image thresholded at 22% of max intensity) and 0.88 for the other (threshold of 14% of max intensity). ConclusionIt was demonstrated that the use of synthetic PET images for histopathological validation allows for bypassing a technically challenging and error-prone step of registering non-invasive PET images with histopathology.

FDG-PET imaging for radiotherapy target volume definition in lung cancer

Multimodality imaging plays a key role in the management of malignant tumours by radiation oncologists. The tumour extension at diagnosis identifies the patients in whom curative-intent radiotherapy is indicated. The target volumes and organs at risk are delineated on the relevant image modality (CT, MRI, PET), co-registered on a CT scan in treatment position for dose calculation purpose. The treatment machines are nowadays able to achieve heterogeneous dose distributions, possibly modulated within the target volume according to variations in the risk of failure. For instance, areas with high initial FDG uptake, low oxygenation, or insufficient response during radiotherapy could become the targets for selective dose increase. The scientific challenge includes registration and iterative segmentation of poorly contrasted images acquired on living bodies (variation in acquisition position, physiological movements and hollow organs filling, signal alteration induced by treatment…). The clinical validation of these innovative approaches and their diffusion in daily routine require a very close collaboration between many disciplines, based on a common language and understanding of radiotherapy target volumes, as illustrated in the present paper with FDG-PET imaging.