Michael Soussan

Tumor Texture Analysis in 18F-FDG PET: Relationships Between Texture Parameters, Histogram Indices, Standardized Uptake Values, Metabolic Volumes, and Total Lesion Glycolysis

Texture indices are of growing interest for tumor characterization in 18F-FDG PET. Yet, on the basis of results published in the literature so far, it is unclear which indices should be used, what they represent, and how they relate to conventional indices such as standardized uptake values (SUVs), metabolic volume (MV), and total lesion glycolysis (TLG). We investigated in detail 31 texture indices, 5 first-order statistics (histogram indices) derived from the gray-level histogram of the tumor region, and their relationship with SUV, MV, and TLG in 3 different tumor types. Methods: Three patient groups corresponding to 3 cancer types at baseline were studied independently: patients with metastatic colorectal cancer (72 lesions), non–small cell lung cancer (24 lesions), and breast cancer (54 lesions). Thirty-one texture indices were studied in addition to SUVs, MV, and TLG, and 5 indices extracted from histogram analysis were also investigated. The relationships between indices were studied as well as the robustness of the various texture indices with respect to the parameters involved in the calculation method (sampling schemes and tumor volume of interest). Results: Regardless of the patient group, many indices were highly correlated (Pearson correlation coefficient |r| ≥ 0.80), making it desirable to focus on only a few uncorrelated indices. Three histogram indices were highly correlated with SUVs (|r| ≥ 0.84). Four texture indices were highly correlated with MV, and none was highly correlated with SUVs (|r| ≤ 0.55). The resampling formula used to calculate texture indices had a substantial impact, and resampling using at least 32 discrete values should be used for texture indices calculation. The texture indices change as a function of the segmentation method was higher than that of peak and maximum SUVs but less than mean SUV for 5 texture indices and was larger than that of MV for 14 texture indices and for the 5 histogram indices. All these results were extremely consistent across the 3 tumor types and explained many of the observations reported in the literature so far. Conclusion: None of the histogram indices and only 17 of 31 texture indices were robust with respect to the tumor-segmentation method. An appropriate resampling formula with at least 32 gray levels should be used to avoid introducing a misleading relationship between texture indices and SUV. Some texture indices are highly correlated or strongly correlate with MV whatever the tumor type. Such correlation should be accounted for when interpreting the usefulness of texture indices for tumor characterization, which might call for systematic multivariate analyses.

Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis.

AbstractWe aimed to clarify the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the management of large-vessel vasculitis (LVV), focusing on 3 issues which are as follows: describe and determine the different FDG-PET criteria for the diagnosis of vascular inflammation, the performance of FDG-PET for the diagnosis of large-vessel inflammation in giant cell arteritis (GCA) patients, and the performance of FDG-PET to evaluate the disease inflammatory activity in Takayasu arteritis (TA) patients.MEDLINE, Cochrane Library, and EMBASE database were searched for articles that evaluated the value of FDG-PET in LVV, from January 2000 to December 2013. Inclusion criteria were American College of Rheumatology criteria for GCA or TA, definition PET positivity threshold, and >4 cases included. Sensitivity (Se) and specificity (Sp) of FDG-PET for the diagnosis of large-vessel inflammation were calculated from each included individual study, and then pooled for meta-analysis with a random-effects model.Twenty-one studies (413 patients, 299 controls) were included in the systematic review. FDG-PET showed FDG vascular uptake in 70% (288/413) of patients and 7% (22/299) of controls. Only vascular uptake equal to or higher than the liver uptake was significantly different between GCA/TA patients and controls (P < 0.001). The meta-analysis of GCA patients (4 studies, 57 patients) shows that FDG-PET has high Se and Sp for the diagnosis of large-vessel inflammation in GCA patients in comparison to controls, with a pooled Se at 90% (95% confidence interval [CI], 79%–93%) and a pooled Sp at 98% (95% CI, 94%–99%). The meta-analysis of TA patients (7 studies, 191 patients) shows that FDG-PET has a pooled Se at 87% (95% CI, 78%–93%) and Sp at 73% (95% CI, 63%–81%) for the assessment of disease activity in TA, with up to 84% Sp, with studies using National Institutes of Health criteria as the disease activity assessment scale.FDG-PET showed good performances in the diagnosis of large-vessel inflammation, with higher accuracy in GCA patients than in TA patients. Although a vascular uptake equal to or higher than the liver uptake appears to be a good criterion for the diagnosis of vascular inflammation, further studies are needed to define the threshold of significance as well as the clinical significance of the vascular uptake.

Relationship between Tumor Heterogeneity Measured on FDG-PET/CT and Pathological Prognostic Factors in Invasive Breast Cancer

Background There is currently little support to understand which pathological factors led to differences in tumor texture as measured from FDG PET/CT images. We studied whether tumor heterogeneity measured using texture analysis in FDG-PET/CT images is correlated with pathological prognostic factors in invasive breast cancer. Methods Fifty-four patients with locally advanced breast cancer who had an initial FDG-PET/CT were retrospectively included. In addition to SUVmax, three robust textural indices extracted from 3D matrices: High-Gray-level Run Emphasis (HGRE), Entropy and Homogeneity were studied. Univariate and multivariate logistic regression was used to identify PET parameters associated with poor prognosis pathological factors: hormone receptor negativity, presence of HER-2 and triple negative phenotype. Receiver operating characteristic (ROC) curves and the (AUC) analysis, and reclassification measures, were performed in order to evaluate the performance of combining texture analysis and SUVmax for characterizing breast tumors. Results Tumor heterogeneity, measured with HGRE, was higher in negative estrogen receptor (p = 0.039) and negative progesterone receptor tumors (p = 0.036), and in Scarff-Bloom-Richardson grade 3 tumors (p = 0.047). None of the PET indices could identify HER-2 positive tumors. Only SUVmax was positively correlated with Ki-67 (p<0.0004). Triple negative breast cancer (TNBC) exhibited higher SUVmax (Odd Ratio = 1.22, 95%CI [1.06–1.39],p = 0.004), lower Homogeneity (OR = 3.57[0.98–12.5],p = 0.05) and higher HGRE (OR = 8.06[1.88–34.51],p = 0.005) than non-TNBC. Multivariate analysis showed that HGRE remained associated with TNBC (OR = 5.27[1.12–1.38],p = 0.03) after adjustment for SUVmax. Combining SUVmax and HGRE yielded in higher area under the ROC curves (AUC) than SUVmax for identifying TNBC: AUC =  0.83 and 0.77, respectively. Probability of correct classification also increased in 77% (10/13) of TNBC and 71% (29/41) of non-TNBC (p = 0.003), when combining SUVmax and HGRE. Conclusions Tumor heterogeneity measured on FDG-PET/CT was higher in invasive breast cancer with poor prognosis pathological factors. Texture analysis might be used, in addition to SUVmax, as a new tool to assess invasive breast cancer aggressiveness.

Tocilizumab in refractory Takayasu arteritis: A case series and updated literature review

BACKGROUND/PURPOSE The aim of this study is to analyze the efficacy and tolerance of tocilizumab in patients with Takayasu arteritis (TA). METHODS We retrospectively studied patients with TA (ACR and/or Ishikawas criteria): 5 French multicenter cases and 39 from the literature. Clinical, biological, radiological disease activity and treatment were analyzed before tocilizumab, during the follow-up and at the last available visit. RESULTS Forty-four patients (median age 26years [3-65];) were included in the present study: 5 patients from the 3 French university hospitals and 39 cases from the literature review. Median follow-up after initiation of tocilizumab was 15months [8-33]. Clinical and biological activities significantly decreased within 3months, similarly to steroid amount (from 15mg/day [5-75] at baseline to 10mg/day [2-30] at 6months; p<0.05) and steroid-dependence rate. Even radiological activity did not significantly decrease at 6months, significant decrease of arterial FDG uptake was noted at 6months. Median duration of tocilizumab treatment was 9months [3-180]. At the last visit, tocilizumab was continued in 17/32 patients (53%), and was discontinued in the 15 remaining cases because of the remission (n=5), relapse (n=3), persistent radiological activity (n=3), cutaneous rash (n=2), severe infection (n=1) and lacking of care welfare system (n=1). No death related to tocilizumab treatment was noted. CONCLUSION This study show the efficacy of tocilizumab in terms of clinical, biological and radiological response, as well as steroid-sparing agent. Only well-designed studies could definitely address the efficacy of tocilizumab in TA.

Comparison of FDG-PET/CT and MR with diffusion-weighted imaging for assessing peritoneal carcinomatosis from gastrointestinal malignancy

ObjectivesTo assess the accuracy of FDG-PET/CT and MR with diffusion-weighted imaging (MR-DWI) for diagnosing peritoneal carcinomatosis (PC) from gastrointestinal malignancies.MethodsThirty consecutive patients referred for staging of gastrointestinal malignancy underwent FDG-PET/CT and MR-DWI in this retrospective study. Extent of PC was characterised by dividing the peritoneal cavity into three sites in each patient: right and left supramesocolic areas and inframesocolic level (total 90 sites). Presence of PC was confirmed either by surgery (18/30) or by follow-up (12/30).ResultsPC was confirmed in 19 patients (19/30). At a total of 90 sites, 27 showed proven PC. On a patient-based analysis, sensitivity, specificity, PPV, NPV and accuracy were respectively 84%, 73%, 84%, 73% and 80% for PET/CT and 84%, 82%, 89%, 75% and 83% for MR-DWI. On a site-based analysis, overall sensitivity and specificity of PET/CT (63%, 90%) and MR-DWI (74%, 97%) were not statistically different (P = 0.27). In the supramesocolic area, MR-DWI detected more sites involved than PET/CT (7/9 vs. 4/9). The sensitivities of PET and MR were lower for subcentimetre tumour implants (42%, 50%). Interobserver agreement was very good for PET/CT and good for MR-DWI.ConclusionsFDG-PET/CT and MR-DWI showed similar high accuracy in diagnosing PC. Both techniques underestimated the real extent of PC because of decreased sensitivity for subcentimetre lesions.Key Points• FDG-PET/CT and MR-DWI showed similar high accuracy for diagnosing peritoneal carcinomatosis.• In the supramesocolic area, MR-DWI could be more sensitive than PET/CT.• Both techniques showed lower sensitivity for subcentimetre lesions.• Interobserver agreement was very good for PET/CT and good for MR-DWI.

Carbodiimide versus Click Chemistry for Nanoparticle Surface Functionalization: A Comparative Study for the Elaboration of Multimodal Superparamagnetic Nanoparticles Targeting αvβ3 Integrins

Superparamagnetic fluorescent nanoparticles targeting αvβ3 integrins were elaborated using two methodologies: carbodiimide coupling and click chemistries (CuACC and thiol-yne). The nanoparticles are first functionalized with hydroxymethylenebisphonates (HMBP) bearing carboxylic acid or alkyne functions. Then, a large number of these reactives functions were used for the covalent coupling of dyes, poly(ethylene glycol) (PEG), and cyclic RGD. Several methods were used to characterize the nanoparticle surface functionalization, and the magnetic properties of these contrast agents were studied using a 1.5 T clinical MRI. The affinity toward integrins was evidenced by solid-phase receptor-binding assay. In addition to their chemoselective natures, click reactions were shown to be far more efficient than the carbodiimide coupling. The grafting increase was shown to enhance targeting affinity to integrin without imparing MRI and fluorescent properties.

FDG-PET/CT in patients with ANCA-associated vasculitis: case-series and literature review.

OBJECTIVES We aimed to assess the clinical value of FDG-PET/CT in patients with ANCA-associated vasculitis. MATERIALS AND METHODS We retrospectively included 16 patients with ANCA-associated vasculitis who underwent 21 FDG-PET/CT between 2009 and 2013, in 2 university hospitals from the Paris suburb area. All FDG-PET/CTs were retrospectively analyzed and compared to clinical, biological and conventional imaging data at baseline and during the follow-up. RESULTS ANCA-associated vasculitis was granulomatosis with polyangiitis (GPA, n=10), microscopic polyangiitis (MPA, n=4), and eosinophilic GPA (EGPA, n=2). PET was performed at initial presentation in 14 cases and during the follow-up in 7 cases. At baseline, PET was positive in 100% of GPA patients (8/8) and in 50% (3/6) of patients with other ANCA-vasculitis (p=0.05). FDG uptake tended to be higher in patients with GPA in comparison to patients with MPA/EGPA (median SUVmax: 5 versus 2.5; p=0.08). Sinonasal, lung, cardio-vascular and kidney involvements were all accurately identified by PET, except in one MPA patient with glomerulonephritis. As expected, skin, joint, eye and peripheral nervous system impairments were not detected by PET. No occult site was detected by PET, except in 2 salivary gland FDG uptake without clinical abnormalities. Patients with GPA exhibited a higher number of positive sites on PET (2 [1.75-2.25] versus 0.5 [0-1], p=0.006) than patients with MPA/EGPA. In pooled data including our study and the literature data of GPA patients (n=31), SUVmax was associated with Birmingham Vasculitis Activity Score (BVAS) (r=0.49; p=0.03). CONCLUSION FDG-PET/CT accurately identifies organ localizations in GPA, other than in nervous system, eye and skin, but do not bring additional benefit to the usual organ screening. The value of FDG-PET/CT in other ANCA-associated vasculitis need to be further addressed.

Diagnosis and localization of renal cyst infection by 18F-fluorodeoxyglucose PET/CT in polycystic kidney disease

Renal cyst infection in polycystic kidney disease is a serious complication. Early diagnosis and localization of infected cyst are crucial and usually require conventional imaging modalities, including ultrasound and computed tomography (CT). However, their contribution is limited because of nonspecific results. We report on a patient with suspected renal cyst infection for which 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan allowed the exact localization of the infected cyst and guided a drainage procedure. FDG-PET/CT imaging could be a valuable tool for early identification of infected renal cyst infection, and may contribute to better patient management.

18F-FDG PET/CT in patients with amyloid light-chain amyloidosis: case-series and literature review.

Objectives: To describe FDG-PET/CT in amyloid light-chain (AL) amyloidosis. Methods: We describe a French multicenter study which included patients with AL amyloidosis who had undergone a FDG-PET/CT during follow-up. Results: Ten patients with AL amyloidosis (median age 62 years [59–85]) were analyzed. AL amyloidosis was of λ-type in 7/10 cases (70%) and localized amyloidosis in 4/10 cases (40%). AL amyloidosis was primary in 7/10 (70%) cases and associated with Waldenstrom’s macroglobulinemia (n = 2) and plasmocytoma (n = 1) in the remaining cases. Median delay between diagnosis and PET was 1 month [0–51]. PET was positive in seven (70%) patients and showed a median FDG SUV of 6.5 [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15]. FDG uptakes with positive PET were localized in seven patients, namely in the nasopharynx (n = 3), bronchopulmonary (n = 2), duodenal, cutaneous, bone, joint and muscular areas (n = 1, each). FDG uptakes on PET were concordant with the known organ impairment in 6/7 cases (86%) and showed unknown nasopharyngeal and mesenteric localization in one case each. PET was negative in the patient with cardiac amyloidosis and two patients with pulmonary amyloidosis. Conclusion: High FDG uptake may be present in patients with AL amyloidosis, however prospective studies are needed in order to determine the place of FDG PET in AL amyloidosis.

Patterns of pulmonary tuberculosis on FDG-PET/CT.

OBJECTIVE This study aims to describe patterns of pulmonary tuberculosis (TB) on FDG-PET/CT. METHODS All patients with a diagnosis of TB and who underwent FDG-PET/CT between January 2009 and June 2010 were included. Clinical, biological and imaging data were reviewed. TB was proven either on bacteriological or histopathological studies (n=13) or on a clinical and imaging basis (n=3). RESULTS Sixteen patients (11 men; median age 56, range 22-84 years) were included. Two distinct patterns were identified. In the lung pattern (9/16), patients had predominantly pulmonary symptoms (6/9 patients, 67%) with a parenchymal involvement: uptakes on lung consolidation ± cavitation surrounded by micronodules. Mediastino-hilar lymph nodes were slightly enlarged (15 mm, 10-27) with moderate uptake (3.9, 2.5-13.4). In the lymphatic pattern (7/16), patients had predominantly systemic symptoms (5/7 cases, 71%) and all had extra-thoracic involvement. Mediastino-hilar lymph nodes were more enlarged (30 mm, 18-35, p=0.03) and with higher uptake (6.8, 5.7-16.8, p=0.034) than in the lung pattern. CONCLUSION We identified two distinct patterns of pulmonary TB on FDG-PET/CT. The lung pattern related to a restricted and slight hypermetabolic infection and the lymphatic pattern related to a systemic and intense infection. Combined interpretation of PET and CT findings improves the specificity of images, especially for the lung pattern.