18F-FDG PET imaging of rheumatoid knee synovitis correlates with dynamic magnetic resonance and sonographic assessments as well as with the serum level of metalloproteinase-3

Purpose The aim of this study was to assess rheumatoid arthritis (RA) synovitis with positron emission tomography (PET) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in comparison with dynamic magnetic resonance imaging (MRI) and ultrasonography (US).Methods Sixteen knees in 16 patients with active RA were assessed with PET, MRI and US at baseline and 4 weeks after initiation of anti-TNF- treatment. All studies were performed within 4 days. Visual and semi-quantitative (standardised uptake value, SUV) analyses of the synovial uptake of FDG were performed. The dynamic enhancement rate and the static enhancement were measured after i.v. gadolinium injection and the synovial thickness was measured in the medial, lateral patellar and suprapatellar recesses by US. Serum levels of C-reactive protein (CRP) and metalloproteinase-3 (MMP-3) were also measured.Results PET was positive in 69% of knees while MRI and US were positive in 69% and 75%. Positivity on one imaging technique was strongly associated with positivity on the other two. PET-positive knees exhibited significantly higher SUVs, higher MRI parameters and greater synovial thickness compared with PET-negative knees, whereas serum CRP and MMP-3 levels were not significantly different. SUVs were significantly correlated with all MRI parameters, with synovial thickness and with serum CRP and MMP-3 levels at baseline. Changes in SUVs after 4 weeks were also correlated with changes in MRI parameters and in serum CRP and MMP-3 levels, but not with changes in synovial thickness.Conclusion ¹⁸F-FDG PET is a unique imaging technique for assessing the metabolic activity of synovitis. The PET findings are correlated with MRI and US assessments of the pannus in RA, as well as with the classical serum parameter of inflammation, CRP, and the synovium-derived parameter, serum MMP-3. Further studies are warranted to establish the place of metabolic imaging of synovitis in RA.     

F-18 FDG whole-body PET for the assessment of disease activity in patients with rheumatoid arthritis

PURPOSE OF REPORT: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used to image synovitis in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate if a simple scoring system based on visual assessment of FDG joint uptake correlates with the clinical assessment of patients with RA undergoing antiinflammatory treatment. MATERIALS AND METHODS: Seven patients with active RA underwent whole-body FDG PET and clinical assessment before and after treatment with the antitumor necrosis factor alpha antibody (infliximab). A PET total joint score, ie, the sum of all scores based on FDG uptake intensity between zero and 4 in 28 joints, was correlated with a total joint score based on the clinical disease activity in the same joints using a Spearman rank correlation. RESULTS: The PET based total joint score was similarly high before onset as was the clinical total joint score. The decrease of FDG joint uptake in the follow-up PET scans correlated significantly with the clinical assessment. Additionally, synovial FDG uptake was found in extraarticular sites such as tendon sheaths and bursae. CONCLUSIONS: Visual assessment of FDG uptake shows a significant correlation with clinical evaluation of disease activity in patients with RA undergoing antiinflammatory treatment.     

Rheumatoid hand joint synovitis: gray-scale and power Doppler US quantifications following anti-tumor necrosis factor-alpha treatment: pilot study

PURPOSE: To evaluate by using B-mode and power Doppler ultrasonography (US) and clinical assessment the response of hand joint synovitis in patients with active rheumatoid arthritis (RA) to treatment with the anti-tumor necrosis factor-alpha agent infliximab. MATERIALS AND METHODS: Wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints in 11 patients with active RA were assessed before and 6 weeks after three infliximab infusions. US assessment was performed at a single site in the MCP and PIP joints and at two sites (radiocarpal and intercarpal) in the wrists. Twenty measurements were performed in the wrists; 110 measurements, in the MCP joints; and 103 measurements, in the PIP joints. Two wrists and seven PIP joints were excluded owing to complete joint destruction. US parameters (synovial thickness, number of US-positive joints [ie, with synovial thickness > or = 1 mm], cumulative synovial thickness index, and presence of Doppler signal) and clinical parameters (swollen joint count) were independently assessed and compared with baseline values by using the McNemar chi2 and paired Student t tests. RESULTS: After infliximab treatment, there was a significant decrease in the mean numbers of swollen and US-positive joints and in the cumulative synovial thickness (P <.05). The mean synovial thickness decreased in all joints swollen at baseline and in the MCP and PIP joints not swollen at baseline (P <.01). Change from baseline cumulative synovial thickness correlated significantly with change in disease activity score (r = 0.69, P <.05). The number of positive Doppler US signals decreased significantly (in 13 US-positive joints at baseline, in five after treatment; P <.05). CONCLUSION: US is a feasible imaging modality for measurement of the response of RA small-joint synovitis to therapy.     

Aortic wall inflammation due to Takayasu arteritis imaged with 18F-FDG PET coregistered with enhanced CT.

The purpose of this study was to evaluate the ability of (18)F-FDG PET to identify aortitis and to localize and follow disease activity in patients with Takayasu arteritis. The value of using (18)F-FDG PET coregistered with enhanced CT in determining vascular lesion sites and inflammatory activity was assessed. METHODS: Takayasu arteritis was diagnosed according to the predefined criteria. Eleven patients with Takayasu arteritis in the active stage, 3 patients with Takayasu arteritis in the inactive stage, and 6 healthy subjects underwent (18)F-FDG PET coregistered with enhanced CT and the inflammatory vascular lesion was evaluated by using the standardized uptake value (SUV) of (18)F-FDG accumulation as an index. Two patients with active disease were analyzed by sequential (18)F-FDG PET scans during treatment. RESULTS: The (18)F-FDG PET revealed intense (18)F-FDG accumulation (SUV > or = 2.7) in the vasculature of 2 of the 11 cases in the active stage of Takayasu arteritis. The other 9 patients in the active stage revealed weak (18)F-FDG accumulation (2.3 > or = SUV > or = 1.2). No significant (18)F-FDG accumulation was observed in the patients with inactive disease (SUV < or = 1.2) and 6 control healthy subjects (SUV < 1.3). Given the cutoff SUV is 1.3, the sensitivity of (18)F-FDG PET analysis of Takayasu arteritis is 90.9% and the specificity is 88.8%. (18)F-FDG PET coregistered with enhanced CT localized (18)F-FDG accumulation in the aortic wall in the patients with Takayasu arteritis who had weak (18)F-FDG accumulation that could not otherwise be identified anatomically. Finally, (18)F-FDG accumulation resolved with therapy in 2 active cases. The disappearance of (18)F-FDG accumulation did not coincide with the level of general inflammatory markers. CONCLUSION: The (18)F-FDG PET images coregistered with enhanced CT images showed the distribution and inflammatory activity in the aorta, its branches, and the pulmonary artery in patients with active Takayasu arteritis, even those who had weak (18)F-FDG accumulation. The intensity of accumulation decreased in response to therapy.     

18F-FDG PET in patients with esophageal squamous cell carcinoma undergoing curative surgery: prognostic implications.

We investigated whether the standardized uptake value (SUV) of the primary tumor, the tumor length measured on a PET image, the number of (18)F-FDG PET-positive nodes, and the PET stage were independent prognostic predictors over other clinical variables in patients with esophageal squamous cell carcinoma who were undergoing curative surgery. METHODS: Sixty-nine patients with newly diagnosed esophageal squamous cell carcinoma who underwent preoperative (18)F-FDG PET and curative esophagectomy were included. The events for survival analysis were defined as recurrence or metastasis and cancer-related death. The disease-free and overall survival rates of each variable were estimated by the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate independent prognostic variables for multivariate survival analysis. RESULTS: Using univariate survival analysis, the presence of adjuvant therapy, pathologic stage, number of CT-positive nodes (0, 1, > or =2), tumor length on PET (cutoff: 3 cm, 5 cm), number of PET-positive nodes (0, 1, 2, > or =3), and PET stage (N0 M0, N1 M0, M1) were significant prognostic predictors for disease-free survival. However, only the number of PET-positive nodes was an independent significant prognostic predictor for disease-free survival in multivariate analysis (hazard ratio = 1.87, P < 0.001). In univariate survival analysis, the sex, presence of adjuvant therapy, clinical and pathologic stages, number of CT-positive nodes, maximum SUV of the primary tumor (cutoff: 6.3, 13.7), tumor length on PET, number of PET-positive nodes, and PET stage were significant prognostic predictors for overall survival. In contrast, the clinical stage (hazard ratio = 0.53, P < 0.05), pathologic stage (hazard ratio = 3.14, P < 0.005), tumor length by PET (hazard ratio = 2.74, P = 0.01), and number of PET-positive nodes (hazard ratio = 1.71, P < 0.05) were independent significant prognostic predictors for overall survival in multivariate analysis. CONCLUSION: In addition to the pathologic stage, (18)F-FDG PET provides noninvasively independent prognostic information using the number of positive lymph nodes and the tumor length on the PET image in preoperative esophageal squamous cell carcinoma. A revised TNM classification system for esophageal carcinoma may consider tumor length and the number of positive lymph nodes as important prognostic factors.     

Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.

18F-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET. Furthermore, the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated. METHODS: Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT, endoscopic ultrasonography, and ultrasound of the neck. In addition, all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity. RESULTS: 18F-FDG PET was able to detect all esophageal cancers, whereas 18F-FLT PET visualized the tumor in 8 of 10 patients. Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients. 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET, whereas 18F-FDG PET showed uptake in benign lesions in 2 patients. The uptake of 18F-FDG (median standardized uptake value [SUV(mean)], 6.0) was significantly higher than 18F-FLT (median SUV(mean), 3.4). Neither 18F-FDG maximum SUV (SUV(max)) nor 18F-FLT SUV(max) correlated with Ki-67 expression in the linear regression analysis. CONCLUSION: In this study, uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake. 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans. Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation.     

The role of Doppler Ultrasonography in evaluating disease activity in a group of juvenile idiopathic arthritis patients

The goal of the study is the evaluation of Power Doppler ultrasound (PDUS) ability to detect the disease activity in juvenile idiopathic artheritis (JIA) patients compared to clinical and biological markers. In forty JIA patients, 1120 joints were assessed clinically and with Doppler ultrasonography. The semi quantitative four grade scale (0–3) was used for grading the PDUS. The disease activity was assessed using the 28-joint Disease Activity Score (DAS28-CRP). Synovitis was detected clinically in 17.5% of examined joints, while ultrasound detected synovitis was found in 18.8%; including 3.5% of clinically normal joints. DAS28-CRP was significantly associated with US findings. Ultrasound evidence of synovial hyperplasia significantly correlated with joint swelling r?=?0.87, while PDUS was significantly correlated with joints tenderness, r?=?0.92. PDUS assessment of synovial vascularization could detect mild disease activity with 100% sensitivity and 75% specificity. Kappa statistics revealed marked agreement (0.83) between tenderness and power Doppler US. Patients showing higher PDUS score (>/=2) are mostly having active disease.

Contrast enhanced gray-scale sonography in assessment of joint vascularity in rheumatoid arthritis: results from the IACUS study group

The purpose of this study way to assess the value of contrast enhanced gray-scale ultrasound (CEUS) in detection of vascularity in joints of patients with rheumatoid arthritis (RA) in a multicenter study of the International Arthritis Contrast Ultrasound (IACUS) study group. We assessed 113 joints in 113 patients (44 men, 69 women; mean age 51±14 years) with clinical diagnosis of RA. Gray-scale ultrasound (US), power Doppler US (PDUS) and CEUS, using a low mechanical index US technique, was performed. CEUS was done by bolus administration of the contrast agent SonoVue (Bracco, Milan, Italy) with a dosage of 4.8-ml SonoVue flushed with 10 ml saline. Detection of joint vascularity was performed for differentiation of active synovitis from inactive intra-articular thickening (synovitis/effusion). With the use of US and PDUS, active synovitis could be differentiated from inactive intra-articular thickening in 68/113 joints (60.1%), whereas CEUS enabled differentiation in 110/113 (97.3%) joints (p<0.0001). Thickness measurement of active synovitis was significantly improved after contrast administration (p=0.008). In conclusion, CEUS improves the differentiation of active synovitis from inactive intra-articular thickening. Since CEUS has shown an ability to improve assessment of vascularized synovial proliferation in RA affected joints, this technique may have further potential in monitoring therapy.     

Dual-time-point 18F-FDG PET for the evaluation of gallbladder carcinoma.

Conventional imaging techniques such as ultrasonography, CT, and MRI are able to detect gallbladder abnormalities but are not always able to differentiate a malignancy from other disease processes such as cholecystitis. The purpose of the present study was to evaluate the efficacy of dual-time-point (18)F-FDG PET for differentiating malignant from benign gallbladder disease. METHODS: The study evaluated 32 patients who were suspected of having gallbladder tumors. (18)F-FDG PET (whole body) was performed at 62 +/- 8 min (early) after (18)F-FDG injection and was repeated 146 +/- 14 min (delayed) after injection only in the abdominal region. We evaluated the (18)F-FDG uptake both visually and semiquantitatively. Semiquantitative analysis using the standardized uptake value (SUV) was performed for both early and delayed images (SUV(early) and SUV(delayed), respectively). The retention index (RI) was calculated according to the equation (SUV(delayed) - SUV(early)) x 100/SUV(early). The tumor-to-liver ratio was also calculated. Results: The final diagnosis was gallbladder carcinoma in 23 patients and benign disease in 9 patients. For visual analysis of gallbladder carcinoma, delayed (18)F-FDG PET images improved the specificity of diagnosis in 2 patients. When an SUV(early) of 4.5, SUV(delayed) of 2.9, and RI of -8 were chosen as arbitrary cutoffs for differentiating between malignant and benign conditions, sensitivity increased from 82.6% to 95.7% and 100% for delayed imaging and combined early and delayed imaging (i.e., RI), respectively. With the same criteria, specificity decreased from 55.6% to 44.4% for delayed imaging and combined early and delayed imaging, respectively. The specificity of (18)F-FDG PET improved to 80% in the group with a normal level of C-reactive protein (CRP) and decreased to 0% in the group with an elevated CRP level. For gallbladder carcinoma, both SUV and tumor-to-liver ratios derived from delayed images were significantly higher than the ratios derived from early images (P < 0.0001). CONCLUSION: Delayed (18)F-FDG PET is more helpful than early (18)F-FDG PET for evaluating malignant lesions because of increased lesion uptake and increased lesion-to-background contrast. However, the diagnostic performance of (18)F-FDG PET depends on CRP levels.     

^18F-FDGPET及PET／CT在风湿性疾病诊断及疗效监测中的应用

^18F-FDGPET及PET／CT检查在风湿性疾病等非肿瘤性疾病中的应用近来受到关注,其独特的糖代谢显像不仅能反映风湿性疾病的活动程度,还可显示全身病变分布范围,有助于风湿性疾病的诊断与鉴别诊断018F-FDG代谢的消失或减低在一定程度上也能够反映风湿性疾病治疗后的缓解情况。笔者对^18F-FDGPET及PET／CT在类风湿关节炎（RA）、血清阴性脊柱关节病（SpA）、大血管炎（LVV）、风湿性多肌痛（PMR）和成人Still病（AOSD）中的应用作一综述。     

Focal thyroid lesions incidentally identified by integrated 18F-FDG PET/CT: clinical significance and improved characterization.

In this retrospective study, we investigated whether the (18)F-FDG uptake pattern and CT findings improved the accuracy over the standardized uptake value (SUV) for differentiating benign from malignant focal thyroid lesions incidentally found on (18)F-FDG PET/CT. We also defined the prevalence of these lesions and their risk for cancer. METHODS: (18)F-FDG PET/CT was performed on 1,763 subjects without a previous history of thyroid cancer from May 2003 to June 2004. Two nuclear medicine physicians and 1 radiologist interpreted PET/CT images, concentrating on the presence of focal thyroid lesions, the maximum SUV of the thyroid lesion, the pattern of background thyroid (18)F-FDG uptake, and the CT attenuation pattern of the thyroid lesion. RESULTS: The prevalence of focal thyroid lesions on PET/CT was 4.0% (70/1,763). Diagnostic confirmation was done on 44 subjects by ultrasonography (US)-guided fine-needle aspiration (n = 29) or US with clinical follow-up (n = 15). Among 49 focal thyroid lesions in these 44 subjects, 18 focal thyroid lesions of 17 subjects were histologically proven to be malignant (papillary cancer in 16, metastasis from esophageal cancer in 1, non-Hodgkin's lymphoma in 1). Therefore, the cancer risk of focal thyroid lesions was 36.7% on a lesion-by-lesion basis or 38.6% on a subject-by-subject basis. The maximum SUV of malignant thyroid lesions was significantly higher than that of benign lesions (6.7 +/- 5.5 vs. 10.7 +/- 7.8; P < 0.05). When only the maximum SUV was applied to differentiate benign from malignant focal thyroid lesions for the receiver-operating-characteristic curve analysis, the area under the curve (AUC) of PET was 0.701. All 16 focal thyroid lesions with very low attenuation or nonlocalization on CT images, or with accompanying diffusely increased thyroid (18)F-FDG uptake, were benign. When those lesions were regarded as benign lesions, irrespective of the maximum SUV, the AUC of PET/CT was significantly improved to 0.878 (P < 0.01). CONCLUSION: Focal thyroid lesions incidentally found on (18)F-FDG PET/CT have a high risk of thyroid malignancy. Image interpretation that includes (18)F-FDG uptake and the CT attenuation pattern, along with the SUV, significantly improves the accuracy of PET/CT for differentiating benign from malignant focal thyroid lesions.     

Correlation of 18F-FDG PET/CT assessments with disease activity and markers of inflammation in patients with early rheumatoid arthritis following the initiation of combination therapy with triple oral antirheumatic drugs

Purpose

This study evaluated the potential of functional imaging to monitor disease activity and response to treatment with disease-modifying antirheumatic drugs (DMARD) in DMARD-naive patients with early rheumatoid arthritis (RA).

Methods

The study involved 17 patients with active RA in whom combination therapy was initiated with methotrexate, sulfasalazine, hydroxychloroquine, and low-dose oral prednisolone. Clinical disease activity was assessed at screening, at baseline and after 2, 4, 8 and 12 weeks of therapy. ¹⁸F-FDG PET/CT of all joints was performed at baseline and after 2 and 4 weeks of therapy.

Results

¹⁸F-FDG maximum standardized uptake values showed a reduction of 22?±?13 % in 76 % of patients from baseline to week 2 and a reduction of 29?±?13 % in 81 % of patients from baseline to week 4. The percentage decrease in ¹⁸F-FDG uptake from baseline to week 2 correlated with clinical outcome, as measured by the disease activity score (DAS-28) at week 12. In addition, changes in C-reactive protein levels and erythrocyte sedimentation rate were positively associated with changes shown by PET.

Conclusion

¹⁸F-FDG PET/CT findings after 2 and 4 weeks of triple combination oral DMARD therapy correlated with treatment efficacy and clinical outcome in patients with early RA. ¹⁸F-FDG PET/CT may help predict the therapeutic response to novel drug treatments.     

Diffuse FDG shoulder uptake on PET is associated with clinical findings of osteoarthritis

OBJECTIVE: Our objective was to examine the degree and pattern of (18)F-FDG uptake within the shoulder as a potential marker of joint inflammation or injury. SUBJECTS AND METHODS: Twenty-four patients undergoing (18)F-FDG PET for clinical oncologic assessment completed questionnaires regarding history of shoulder disease, trauma, pain, and/or functional impairment. Thorough physical examination of the shoulder was performed. A clinical diagnosis of specific shoulder derangement or normal was established for each patient. PET scans were evaluated blindly by a nuclear medicine physician and a musculoskeletal radiologist qualitatively for location, distribution, and intensity of shoulder uptake. Standardized uptake values (SUV) were measured. RESULTS: Twenty-one patients had shoulder PET findings. Fourteen had clinical findings consistent with a specific diagnosis in the PET-positive shoulder. The remaining seven PET-positive patients were clinically normal. Three recognizable patterns of uptake were appreciable. Eight of 10 patients with diffuse uptake had findings of osteoarthritis (n = 7) or bursitis (n = 1). Two of four patients with focal greater tuberosity uptake had findings of rotator cuff injury. Two of four patients with focal glenoid uptake had findings of frozen shoulder. SUV showed a positive correlation with subject age (p < 0.01), but no association with clinical findings was identified. CONCLUSION: The pattern of FDG uptake within the shoulder may point to specific clinical entities. While focal uptake is less reliably related to clinical findings, diffuse uptake is associated with signs and symptoms of osteoarthritis or bursitis.     

18F-FDG uptake as a biologic prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer.

Among patients with resected non-small cell lung cancer (NSCLC), approximately 50% present with a recurrent tumor. The clinical or pathologic TNM staging does not always provide a satisfactory explanation for differences in relapse and survival. Thus, it is of major importance to be able to predict these relapses and to prevent them with an active chemotherapy or radiotherapy program (or both). 18F-FDG uptake on PET could be of prognostic significance in patients with resected NSCLC. The goal of this study was to determine whether the level of metabolic activity observed with 18F-FDG uptake correlates with the probability of postoperative recurrence in patients with NSCLC. METHODS: Fifty-seven patients with NSCLC were examined with 18F-FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high-SUV (> 5.0) and low-SUV (< or = 5.0) groups. All patients underwent thoracotomy within 4 wk after the 18F-FDG PET study. Tumor 18F-FDG uptake (SUV), pathologic stage, and lesion size were analyzed for their possible association with disease-free survival. RESULTS: Forty-six patients had pathologic stage I NSCLC and 11 had pathologic stage II or stage III NSCLC. In a univariate analysis, patients with an SUV of < or = 5 had a much better disease-free survival than did patients with an SUV of > 5 (P < 0.0001). In patients with pathologic stage I and stage IA NSCLC, the SUV was also correlated with disease-free survival (P < 0.0001 and P = 0.0012, respectively). Patients with pathologic stage I disease had an expected 5-y disease-free survival rate of 88% if the SUV was < or = 5 and a survival rate of < or = 17% if the SUV was > 5. A multivariate Cox analysis identified the SUV as the most significant independent factor for disease-free survival. CONCLUSION: We conclude that the 18F-FDG uptake in primary NSCLC determined by PET has a significant independent postoperative prognostic value for recurrence, especially in patients with pathologic stage I NSCLC. 18F-FDG uptake was superior to pathologic stage in predicting relapse of patients with NSCLC.     

Usefulness of fasting 18F-FDG PET in identification of cardiac sarcoidosis.

Cardiac PET using (18)F-FDG under fasting conditions (fasting (18)F-FDG PET) is a promising technique for identification of cardiac sarcoidosis and assessment of disease activity. The aim of this study was to investigate the usefulness of fasting (18)F-FDG PET in detecting inflammatory lesions of cardiac sarcoidosis from a pathophysiologic standpoint. METHODS: Twenty-two patients with systemic sarcoidosis were classified into 2 groups of 11 each according to the presence or absence of sarcoid heart disease. Cardiac sarcoidosis was diagnosed according to the Japanese Ministry of Health and Welfare guidelines for diagnosing cardiac sarcoidosis with the exception of scintigraphic criteria. Nuclear cardiac imaging with fasting (18)F-FDG PET, (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT, and (67)Ga scintigraphy were performed in all patients. PET and SPECT images were divided into 13 myocardial segments and the standardized uptake value (SUV) of (18)F-FDG was calculated and defect scores (DS) for (99m)Tc-MIBI uptake were assessed for each segment. The total SUV (T-SUV) and total DS (TDS) were calculated as the sum of measurements for all 13 segments, and the diagnostic accuracy of fasting (18)F-FDG PET was compared with that of the other nuclear imaging modalities. In addition, pathophysiologic relationships between inflammatory activity and myocardial damage were examined by segmental comparative study using the SUV and DS. RESULTS: In patients with cardiac sarcoidosis, fasting (18)F-FDG PET revealed a higher frequency of abnormal myocardial segments than (99m)Tc-MIBI SPECT (mean number of abnormal segments per patient: 6.6 +/- 3.0 vs. 3.0 +/- 3.2 [mean +/- SD], P < 0.05). The sensitivity of fasting (18)F-FDG PET in detecting cardiac sarcoidosis was 100%, significantly higher than that of (99m)Tc-MIBI SPECT (63.6%) or (67)Ga scintigraphy (36.3%). The accuracy of fasting (18)F-FDG PET was significantly higher than (67)Ga scintigraphy. The T-SUV demonstrated a good linear correlation with serum angiotensin-converting enzyme levels (r = 0.83, P < 0.01), and the TDS showed a significant negative correlation with the left ventricular ejection fraction (r = -0.82, P < 0.01). In abnormal myocardial segments on the nuclear scan, the SUV showed a significant negative correlation with the DS (r = -0.63, P < 0.0001). CONCLUSION: This study suggests that fasting (18)F-FDG PET can detect the early stage of cardiac sarcoidosis, in which fewer perfusion abnormalities and high inflammatory activity are noted, before advanced myocardial impairment.     

Early 18F-FDG PET for prediction of prognosis in patients with diffuse large B-cell lymphoma: SUV-based assessment versus visual analysis.

The purpose of this study was to assess the prognostic value of early (18)F-FDG PET using standardized uptake value (SUV) compared with visual analysis in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Ninety-two patients with newly diagnosed DLBCL underwent (18)F-FDG PET prospectively before and after 2 cycles of chemotherapy (at midtherapy). Maximum SUV (SUVmax) and mean SUV (SUVmean) normalized to body weight and body surface area, as well as tumor-to-normal ratios, were computed on the most intense uptake areas. The SUVs, tumor-to-normal ratios, and their changes over time were compared with visual analysis for predicting event-free survival (EFS) and overall survival, using receiver-operating-characteristic (ROC) analysis. Survival curves were estimated with Kaplan-Meier analysis and compared using the log-rank test. RESULTS: With visual analysis, the accuracy of early PET to predict EFS was 65.2%. The 2-y estimate for EFS was 51% (95% confidence interval [CI], 34%-68%) in the PET-positive group compared with 79% (95% CI, 68%-90%) in the PET-negative group (P = 0.009). An optimal cutoff value of 65.7% SUVmax reduction from baseline to midtherapy obtained from ROC analysis yielded an accuracy of 76.1% to predict EFS. The 2-y estimate for EFS was 21% (95% CI, 0%-42%) in patients with SUVmax reduction 65.7% (P < 0.0001). Fourteen patients considered as positive on visual analysis could have been reclassified as good responders. CONCLUSION: SUV-based assessment of therapeutic response during first-line chemotherapy improves the prognostic value of early (18)F-FDG PET compared with visual analysis in DLBCL.     

Characterization of the normal adrenal gland with 18F-FDG PET/CT.

Prior studies have documented increased (18)F-FDG adrenal activity in both benign and malignant pathologic conditions. When whole-body PET imaging is performed without CT anatomic coregistration, however, the normal adrenal gland is difficult to recognize. The purpose of this study was to investigate the normal adrenal appearance and standardized uptake value (SUV) using (18)F-FDG PET/CT imaging. METHODS: Twenty patients with lymphoma with normal-appearing adrenal glands on prior CT examination (less than a 5% pretest likelihood of adrenal involvement) were studied. PET/CT imaging was performed 2 h after intravenous administration of (18)F-FDG. Unenhanced CT scans were acquired for attenuation correction and anatomic coregistration. PET images were reconstructed using an ordered-subsets expectation maximization algorithm and were corrected for body weight, dose, and radioactive decay. Ability to confirm visualization of the adrenal glands was determined for (18)F-FDG PET alone and for (18)F-FDG PET/CT by a consensus of 2 readers, and uptake of (18)F-FDG in the adrenal gland was compared with liver activity and scored visually (0 = no visualization, 1 = activity less than in liver, 2 = activity equal to liver activity, and 3 = activity greater than in liver). RESULTS: The 2 readers agreed on visualization of the adrenal glands with PET alone for 2 of 40 (5%) glands. With PET/CT, the readers agreed on visualization of 27 of 40 (68%) adrenal glands. Visual scores for normal adrenal activity ranged from 0 to 3, and maximum SUVs ranged from 0.95 to 2.46. Visual scoring of adrenal activity correlated well with both mean and maximal SUV (mean SUV vs. visual score: slope = 0.96, r = 0.88; maximum SUV vs. visual score: slope = 0.99, r = 0.87). CONCLUSION: PET/CT permits more reliable visualization of normal adrenal glands than does PET alone. Visual assessment of adrenal uptake correlates well with SUV measurement, and readers of PET/CT need to be aware of the wide range of normal adrenal uptake.     

Spatial and temporal heterogeneity of regional myocardial uptake in patients without heart disease under fasting conditions on repeated whole-body 18F-FDG PET/CT.

Imaging of cardiac (18)F-FDG uptake is used in the diagnostic evaluation of residual viable myocardium. Although, originally, hibernating myocardium was identified by a mismatch between perfusion defect and relatively preserved (18)F-FDG uptake, at present several studies propose that (18)F-FDG distribution can also be used alone for this purpose. Nevertheless, even severe myocardial (18)F-FDG uptake defects are frequently observed in cancer patients without any cardiac disease. The aim of this study was to retrospectively analyze global and regional (18)F-FDG cardiac images of 49 consecutive cancer patients free of cardiac diseases who submitted to 3 PET scans under fasting conditions. METHODS: Images were acquired with a high-resolution PET/CT scanner. Three-dimensional regions of interest were drawn on the fused PET/CT images to measure the maximal standardized uptake value of the left ventricular myocardium (SUV(Myo)) as well as the average SUV of the left ventricular blood (SUV(LV)) and of the liver (SUV(Liver)). Analysis of regional myocardial (18)F-FDG uptake was performed on a subsample of 26 patients by an automatic recognition of endocardial and epicardial borders and subdividing the left ventricle in 20 segments. Regional (18)F-FDG distribution was defined as the percentage of SUV(Myo) in each region. RESULTS: SUV(Myo) as well as SUV(LV) and SUV(Liver) did not change on average throughout the studies. This stability was not caused by a persistent pattern of myocardial (18-)FDG distribution. Rather, it was associated with important variations in both directions over time. Regional (18)F-FDG distribution was largely heterogeneous in all 3 studies, with a variation coefficient in each patient of 18% +/- 7%, 18% +/- 5%, and 17% +/- 5%, respectively. An (18)F-FDG uptake of <50% occurred in 78, 102, and 69 of 468 segments, although it disappeared in 55% of instances at subsequent examinations. Regional temporal variability was also marked: The absolute value of the difference in percent uptake was 10.1% +/- 7.3% from test 1 to test 2, 8.0% +/- 7.0% from test 1 to test 3, and 9.2% +/- 6.9% from test 2 to test 3. Overall from one test to another, uptake increased or decreased by >10% in 76 and in 116 of 468 segments, respectively. CONCLUSION: The large spatial and temporal heterogeneity of the myocardial metabolic pattern, in cancer patients free of any disease, suggests a word of caution on the use of (18)F-FDG alone as a diagnostic tool for myocardial viability.     

Accuracy of PET for diagnosis of solid pulmonary lesions with 18F-FDG uptake below the standardized uptake value of 2.5.

Benign and malignant pulmonary lesions usually are differentiated by 18F-FDG PET with a semiquantitative 18F-FDG standardized uptake value (SUV) of 2.5. However, the frequency of malignancies with an SUV of <2.5 is significant, and pulmonary nodules with low 18F-FDG uptake often present diagnostic challenges. METHODS: Among 360 consecutive patients who underwent 18F-FDG PET to evaluate pulmonary nodules found on CT, we retrospectively analyzed 43 who had solid pulmonary lesions (excluding lesions with ground-glass opacity, infiltration, or benign calcification) with an SUV of <2.5. The uptake of 18F-FDG was graded by a visual method (absent, faint, moderate, or intense) and 2 semiquantitative methods (SUV and contrast ratio [CR]). Final classification was based on histopathologic findings or at least 6 mo of clinical follow-up. RESULTS: We found 16 malignant (diameter, 8-32 mm) and 27 benign (7-36 mm) lesions. When faint visual uptake was the cutoff for positive 18F-FDG PET results, the receiver-operating-characteristic (ROC) analysis correctly identified all 16 malignancies and yielded false-positive results for 10 of 27 benign lesions. Sensitivity was 100%, specificity was 63%, and the positive and negative predictive values were 62% and 100%, respectively. When an SUV of 1.59 was the cutoff for positive 18F-FDG PET results, the ROC analysis revealed 81% sensitivity, 85% specificity, and positive and negative predictive values of 77% and 89%, respectively. At a cutoff for positive 18F-FDG PET results of a CR of 0.29, the ROC analysis revealed 75% sensitivity, 82% specificity, and positive and negative predictive values of 71% and 85%, respectively. The areas under the curve in ROC analyses did not differ significantly among the 3 analyses (visual, 0.84; SUV, 0.81; and CR, 0.82). Analyses of intra- and interobserver variabilities indicated that visual and SUV analyses were quite reproducible, whereas CR analysis was poorly reproducible. CONCLUSION: These results suggested that for solid pulmonary lesions with low 18F-FDG uptake, semiquantitative approaches do not improve the accuracy of 18F-FDG PET over that obtained with visual analysis. Pulmonary lesions with visually absent uptake indicate that the probability of malignancies is very low. In contrast, the probability of malignancy in any visually evident lesion is about 60%.     

Quantification of synovial and erosive changes in rheumatoid arthritis with ultrasound—Revisited

Synovitis is a predictive factor of irreversible changes in the joints, tendons, and ligaments in patients with rheumatoid arthritis (RA). Therefore, the early demonstration of reversible, pre-erosive inflammatory features to diagnose RA, the monitoring of disease activity, and the response to therapy are of great importance. Technical developments in ultrasound now allow the quantification of synovitis and erosions, and enable the assessment and follow-up of disease activity. However, both the subjective and objective quantification techniques are associated with different problems. This review article highlights the advantages and disadvantages of sonographic quantification, and revisits the somewhat controversial positions apparent in the current literature. Familiarity with the imaging findings and the scoring systems used to characterize erosive changes are prerequisites for considerably improving the detection and monitoring of synovitis and erosions. The role of ultrasound in the diagnostic approach to RA, particularly in the quantification of synovial and erosive changes, will be explored and the current literature will be reviewed.