Implementation of xSPECT, xSPECT bone and Broadquant from literature, clinical survey and innovative phantom study with task-based image quality assessment.

OBJECTIVE: From patient and phantom studies, we aimed to highlight an original implementation process and share a two-years experience clinical feedback on xSPECT (xS), xSPECT Bone (xB) and Broadquant quantification (Siemens) for 99mTc-bone and 177Lu-NET (neuroendocrine tumors) imaging. METHODS: Firstly, we checked the relevance of implemented protocols and Broadquant module on the basis of literature and with a homogeneous phantom study respectively. Then, we described xS and xB behaviours with reconstruction parameters (10i-0mm to 40i-20mm) and optimized the protocols through a blinded survey (7 physicians). Finally, the preferred 99mTc-bone reconstruction was assessed through an IEC NEMA phantom including liquid bone spheres. Conventional SNR, CNR, spatial resolution, Q.%error, and recovery curves; and innovative NPS, TTF and detectability score d' were performed (ImQuest software). We also sought to review the adoption of these tools in clinical routine and showed the potential of quantitative xB in the context of theranostics (Xofigo®). RESULTS: We showed the need of optimization of implemented reconstruction algorithms and pointed out a decay correction particularity with Broadquant. Preferred parameters were 1s-25i-8mm and 1s-25i-5mm for xS/xB-bone and xS-NET imaging respectively. The phantom study highlighted the different image quality especially for the enhanced spatial resolution xB algorithm (1/TTF10%=2.1 mm) and showed F3D and xB shared the best performances in terms of image quality and quantification. xS was generally less efficient. CONCLUSIONS: Qualitative F3D still remains the clinical standard, xB and Broadquant offer challenging perspectives in theranostics. We introduced the potential of innovative metrics for image quality analysis and showed how CT tools should be adapted to fit nuclear medicine imaging.

Assessment of the Association between Entropy in PET/CT and Response to Anti-PD-1/PD-L1 Monotherapy in Stage III or IV NSCLC.

Anti-PD-1/PD-L1 therapy indications are broadened in non-small cell lung cancer (NSCLC) although immune checkpoint inhibitors (ICI) do not provide benefits for the entire population. Texture features based on positron emission tomography/computed tomography (PET/CT), especially entropy (based on a gray-level co-occurrence matrix (GLCM)), could be interesting as predictors in NSCLC. The aim of our retrospective study was to evaluate the association between GLCM-entropy and response to anti-PD-1/PD-L1 monotherapy at the first evaluation in stage III or IV NSCLC, comparing patients with progressive disease (PD) and non-progressive disease (non-PD). In total, 47 patients were included. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) were used to evaluate the response to ICI treatment (nivolumab, pembrolizumab, or atezolizumab). At the first evaluation, 25 patients were PD and 22 were non-PD. GLCM-entropy was not predictive of response at the first evaluation. Furthermore, GLCM-entropy was not associated with progression-free survival (PFS) (p = 0.393) or overall survival (OS) (p = 0.220). Finally, GLCM-entropy measured in PET/CT performed before ICI initiation in stage III or IV NSCLC was not predictive of response at the first evaluation. However, this study demonstrates the feasibility of using texture parameters in routine clinical practice. The interest of measuring PET/CT texture parameters in NSCLC remains to be evaluated in larger prospective studies.

Orbital Metastasis: A Rare but Typical Location of Small Intestine Neuroendocrine Tumor on 18F-FDOPA PET/CT.

ABSTRACT: Orbital foci of increased uptake are sometimes visualized on 18F-FDOPA PET/CT, but the literature remains poor as to their nature. The orbit is indeed a rare site of metastatic involvement. Given this low probability of metastatic location, the question of an incidental benign finding may arise. We reviewed all 18F-FDOPA PET/CT examinations performed at our institution between January 2015 and May 2021: 4/149 patients presented at least 1 orbital focus of increased uptake, all of them presented a metastatic small intestine neuroendocrine tumor. Somatostatin receptor expression was confirmed using 68Ga-DOTATOC PET/CT supporting the hypothesis of genuine metastases.

Performances of 18F-FDOPA PET/CT in the Preoperative Evaluation of the Peritoneal Cancer Index in Small Intestine Neuroendocrine Tumors.

PURPOSE: Peritoneal carcinomatosis (PC) concerns up to 30% of patients with a neuroendocrine tumor (NET), especially of the small intestine. Aggressive management of carcinomatosis seems to be justified, especially with regard to possible mechanical complications. 18F-FDOPA PET/CT is known to be the most sensitive imaging modality for the detection of small bowel NET metastases, yet its performance in the detection of PC is not well studied. The main objective of our study is to evaluate the performances of preoperative 18F-FDOPA PET/CT in the prediction of surgical peritoneal cancer index. METHODS: All patients referred to our center for an 18F-FDOPA PET/CT from October 2017 to January 2021 were retrospectively screened. Images were analyzed by a blinded nuclear medicine physician, and peritoneal abnormalities were reported to comply with the surgical peritoneal cancer index standard. Per patient analysis and per region analysis were then conducted. RESULTS: Thirty-three patients were included; 6 patients (35 regions) presented a peritoneal carcinosis. Peritoneal Carcinomatosis Index (PCI) estimated on 18F-FDOPA PET/CT was significantly and strongly correlated to surgical PCI (r = 0.96, P < 0.001). Patient-based sensitivity, specificity, negative predictive value, and positive predictive value for 18F-FDOPA PET/CT were 100%, 93%, 100%, and 75%, respectively. The agreement between 18F-FDOPA and surgery regarding PC was excellent (Cohen κ = 0.82 on per patient analysis, 0.74 on per region analysis). CONCLUSIONS: A preoperative estimation of PCI is achievable based on 18F-FDOPA PET/CT for small intestine NET and could allow to optimize surgical procedures and patient selection.

Predicting subacute hematological toxicity of 177Lu-DOTATATE therapy using healthy organs' uptake on post-treatment quantitative SPECT: A pilot study.

The aim is to investigate the usefulness of 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE) healthy organs' (spleen, kidneys, bone marrow) standard uptake value for the prediction of subacute hematological toxicity in patients undergoing 177Lu-DOTATATE treatment. All patients referred from January 2021 to May 2022 for 177Lu-DOTATATE treatment were retrospectively screened. For each treatment session, baseline clinical data including age, sex, weight, delay between 177Lu-DOTATATE treatment and last cold somatostatin analogue intake were collected. Mean standardized uptake value (SUVmean) of healthy organs was measured and analyzed by generalized linear mixed effect models. Outcomes (significant decrease of platelets, hemoglobin levels and neutrophils) were assessed 1 month later, considering their within-subject biological coefficient of variation, published by the European Federation of Clinical Chemistry and Laboratory Medicine. A total of 9 patients (33 treatment sessions) were included. No predictive factors were identified for platelet and neutrophil decrease. Splenic SUVmean was found to be a significant predictor of hemoglobin levels decrease. Using an optimal threshold of ≥6.22, derived sensitivity and specificity to predict hemoglobin decrease were 85.7% [46.4; 99.0] and 76.9% [57.5; 89.2] respectively with an accuracy of 82.4%. Although not significantly predictive of hematological toxicity, bone marrow SUVmean and renal SUVmean were correlated with splenic SUVmean. Quantitative single photon emission computed tomography and healthy organs analysis might help to foresee hematological subacute toxicity in patients undergoing 177Lu-DOTATATE treatment and improve patient management.

Pulmonary cavitations with increased 18F-FDG uptake revealing a thoracic endometriosis: A case report.

RATIONALE: Thoracic endometriosis is a rare disorder that can involve airways, pleura and lung parenchyma. It is the most frequent form of extra-abdominopelvic endometriosis. Multiple lung cavitations are a rare feature of thoracic endometriosis. PATIENT CONCERNS: A 46-year-old woman was referred to our hospital after incidental finding of multiple pulmonary cavitations with surrounding areas of ground glass opacity on a thoraco-abdominal computed tomography-scan performed for abdominal pain. Retrospectively, the patient also reported mild hemoptysis occurring 4 months ago. DIAGNOSES: Positron emission tomography-computed tomography scan revealed moderate and homogeneous [18F] fluoro-2-deoxy-D-glucose (18F-FDG) uptake in pulmonary cavitations (maximum standardized uptake value 5.7). The diagnosis of thoracic endometriosis was confirmed by histological examination of surgical resection of a left lower lobe cavitation. INTERVENTIONS AND OUTCOME: Gonadotropin-releasing hormone analogues associated with add-back therapy was started. Four months after initiating pharmacological treatment, the chest computed tomography-scan showed a dramatic decrease in lung cavitations size. LESSONS: Thoracic endometriosis is a rare disorder requiring a multidisciplinary management including gynaecologist, pulmonologist, radiologist, nuclear physician, pathologist and thoracic surgeon for early diagnosis and treatment. Our case report highlights that an increased 18F-FDG uptake can be found in thoracic endometriosis syndrome presenting as multiple lung cavitations.

18F-FDG cerebellum/liver index as a prognostic factor for progression-free survival in diffuse large B-cell lymphoma.

OBJECTIVE: 18F-FDG PET/CT provides valuable informations regarding the prognosis of DLBCL. The aim of this study is to test a novel index based on cerebellar uptake to predict progression free survival in DLBCL patients. METHODS: Data from patients with de novo DLBCL between January 2011 and December 2018 were retrospectively collected and PFS was determined. The conventional PET parameters (SUVmax and total metabolic tumor volume) and the CLIP, corresponding to the ratio of the cerebellum SUVmax over the liver SUVmean, were extracted from baseline 18F-FDG PET. RESULTS: Ninety-five patients were included. When using a threshold of 3.24, CLIP was a significant predictor of PFS on univariate analysis (HR 3.4, p < 0.001) with different 5-year survival rates: 68% (CLIP ≥ 3.24) versus 32% (CLIP < 3.24). Multivariate analysis confirmed the prognostic value of CLIP, as it is one of the two factors remaining significant with ß2-microglobulin (HR 2.1 and 2.5 respectively, p = 0.04 and p = 0.03). A score associating ß2-microglobulin and CLIP allowed to separate the population into three groups of different outcome in terms of 5-year PFS: low risk (80%), intermediate risk (42%) and high risk (17%). CONCLUSIONS: The CLIP derived from pre-therapeutic 18F-FDG PET seems to be an interesting predictive marker of PFS in DLBCL treated by immunochemotherapy.

Superiority of NaF PET/CT Over Chest CT in a Case of Osteosarcoma.

ABSTRACT: We report the case of a 21-year-old man referred to our institution for the initial staging of an osteoblastic osteosarcoma of the right femur. An 18F-NaF PET/CT demonstrated millimetric pleuroparenchymal metastases, later confirmed on follow-up. These lesions were not reported on both dedicated chest CT and 18F-FDG PET/CT.

Vanishing Bone Metastases in 18F-FDG PET/CT.

A 36-year-old woman with a history of large B-cell lymphoma was referred for the exploration of sclerotic bone thoracic vertebral metastases discovered on a contrast-enhanced CT examination. F-FDG PET showed no pathological uptake in the affected vertebrae, as well as normal vertebral density on the coupled unenhanced CT. After review of the initial contrast-enhanced CT, a left brachiocephalic vein stenosis was noted, leading to a retrograde contrast filling of the accessory hemiazygos vein and the capillary spaces within the vertebrae, mimicking sclerotic metastases.

18FDG PET/CT in Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type.

An 86-year-old woman was referred for a rare but aggressive subtype of primary cutaneous lymphoma of the right lower limb: diffuse large B-cell lymphoma leg type. Initial evaluation by whole-body F-FDG PET/CT showed intense hypermetabolic activity of multiple cutaneous and subcutaneous nodules of the distal third of the right leg. Follow-up evaluations by F-FDG PET/CT showed complete response after 4 and 8 cycles of appropriate rituximab combination with polychemotherapy. Although no specific recommendations are available, our case stresses the major role of F-FDG PET/CT for initial extension and treatment response evaluation in clinical practice of primary cutaneous diffuse large B-cell lymphoma leg type.

PET/CT of Duodenal Gangliocytic Paraganglioma.

An 87-year-old woman with leg-type lymphoma underwent a staging F-FDG PET/CT, which demonstrated besides leg lymphomatous lesions a round, well-defined, preduodenal mass with moderate FDG uptake. This mass remained unchanged after chemotherapy treatment completion, despite a complete metabolic response of lymphomatous lesions. A biopsy revealed a gangliocytic paraganglioma. Subsequent F-FDOPA PET/CT and somatostatin receptor scintigraphy were positive and did not depict any other lesions.

Added value of 18F-fluorocholine positron emission tomography-computed tomography in presurgical localization of hyperfunctioning parathyroid glands after dual tracer subtraction scintigraphy failure: A retrospective study of 47 patients.

Hyperparathyroidism is a common endocrine disorder. The precise localization of causal parathyroid gland is crucial to guide surgical treatment. Several studies report the added value of 18F-fluorocholine (FCH) positron emission tomography-computed tomography (PET/CT) as second line imaging but rely on suboptimal first-line imaging using 99mTc-sestaMIBI dual phase scintigraphy. The aim of this study is to evaluate the percentage of successful parathyroid localization with FCH PET/CT after failure of a more sensitive first-line detection protocol associating neck ultrasonography and 99mTc-Pertechnetate/99mTc-sestaMIBI dual tracer subtraction scintigraphy.We included retrospectively 47 patients who underwent a FCH PET/CT as second line imaging for biologically proven primary hyperparathyroidism from November 2016 to October 2018 in Godinot Institute (Reims, France). 99mTc-Pertechnetate/99mTc-sestaMIBI dual tracer subtraction scintigraphy and neck ultrasonography were used as first-line imaging and failed to localize the causal parathyroid lesion in all cases.FCH PET/CT demonstrated at least 1 parathyroid target lesion in 29 patients (62%). 21/29 patients underwent surgery. Target lesions corresponded histologically to hyperfunctioning parathyroid glands for all 21 patients and surgery was followed by hyperparathyroidism biological resolution. Calcium serum levels were associated to FCH PET/CT positivity (P = .002) and a trend toward significance was seen for Parathyroid hormone (PTH) levels (P = .09).FCH PET/CT is a promising tool in second-line parathyroid imaging. Large prospective studies and cost-effectiveness analyses are needed to precise its role.

A no-reference respiratory blur estimation index in nuclear medicine for image quality assessment.

Few indexes are available for nuclear medicine image quality assessment, particularly for respiratory blur assessment. A variety of methods for the identification of blur parameters has been proposed in literature mostly for photographic pictures but these methods suffer from a high sensitivity to noise, making them unsuitable to evaluate nuclear medicine images. In this paper, we aim to calibrate and test a new blur index to assess image quality.Blur index calibration was evaluated by numerical simulation for various lesions size and intensity of uptake. Calibrated blur index was then tested on gamma-camera phantom acquisitions, PET phantom acquisitions and real-patient PET images and compared to human visual evaluation.For an optimal filter parameter of 9, non-weighted and weighted blur index led to an automated classification close to the human one in phantom experiments and identified each time the sharpest image in all the 40 datasets of 4 images. Weighted blur index was significantly correlated to human classification (ρ = 0.69 [0.45;0.84] P < .001) when used on patient PET acquisitions.The provided index allows to objectively characterize the respiratory blur in nuclear medicine acquisition, whether in planar or tomographic images and might be useful in respiratory gating applications.

Data-driven respiratory gating for ventilation/perfusion lung scan.

BACKGROUND: Ventilation/perfusion lung scan is subject to blur due to respiratory motion whether with planar acquisition or single photon emission computed tomography (SPECT). We propose a data-driven gating method for extracting different respiratory phases from lung scan list-mode or dynamic data. METHODS: The algorithm derives a surrogate respiratory signal from an automatically detected diaphragmatic region of interest. The time activity curve generated is then filtered using a Savitzky-Golay filter. We tested this method on an oscillating phantom in order to evaluate motion blur decrease and on one lung SPECT. RESULTS: Our algorithm reduced motion blur on phantom acquisition: mean full width at half maximum 8.1 pixels on non-gated acquisition versus 5.3 pixels on gated acquisition and 4.1 pixels on reference image. Automated detection of the diaphragmatic region and time-activity curves generation were successful on patient acquisition. CONCLUSIONS: This algorithm is compatible with a clinical use considering its runtime. Further studies will be needed in order to validate this method.

Everolimus-induced pulmonary toxicity: Findings on 18F-FDG PET/CT imaging.

The everolimus-exemestane combination is indicated in advanced breast cancer treatment and usually well tolerated. The objective of the study was to determine the frequency of everolimus lung side effects and investigate their imaging characteristics on positron emission tomography with 18F-fluoro-deoxy-glucose combined with computerized tomography (F-FDG PET/CT).Our single-center retrospective descriptive study systematically included all patients with metastatic breast cancer treated by this combination (n = 29 representing 57 F-FDG PET/CT). Number of segments involved was quantified. Maximum standardized uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic target volume (MTV), and total lesion glycolysis (TLG) were measured. Severe pneumopathy was studied by subgroup analysis.Pleuroparenchymal anomalies rate detected on F-FDG PET/CT was 62%. Alveolar-interstitial lesions were mainly observed (89%) and affected 2.8 segments (0.5-11.5) with a median of 2 segments. S7 and S10 were the most involved segments with SUVmax 3.9 (1.3-8.8) and SUVmean 2.2 (0.7-4.9). Statistically significant difference (P = .02) was found with number of segment involved to characterize severe pneumopathy (average of 6.3 segments [2.5-11.5] vs 1.9 segments [0.5-8] for interstitial lung disease) but not with SUVmax, SUVmean, MTV, TLG (P = .14, 0.22, 0.22, and 0.17, respectively).The F-FDG PET/CT could highlight pulmonary everolimus side effects, with a typical imaging pattern: alveolar-interstitial opacities associated with moderate uptake, more or less extensive, mainly affecting the lower lobes. Rarely, a pseudotumoral aspect may be detected, corresponding to a pitfall. MTV or TLG showed a tendency to differentiate severe pneumopathy vs interstitial lung disease but no statistically significant differences was observed contrarily to the number of segments involved. Further studies are necessary to determine if the F-FDG PET/CT could early predict adverse effects of mTOR inhibitors.

18F-FDG PET/CT Evaluation of Ceritinib Therapy in Metastatic ALK-Positive Non-small Cell Lung Cancer.

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancers (NSCLC) account for 3% to 7% of all NSCLC and require a standard treatment by crizotinib. However, crizotinib resistance is frequent within the first 12 months of treatment. Ceritinib is a novel tyrosine kinase inhibitor of ALK recently introduced in France for metastatic or locally advanced crizotinib-resistant ALK NSCLC. We report the first use of ceritinib in our institution with a spectacular tumoral response after only 3 months of treatment. This case demonstrates the major role of F-FDG PET/CT for monitoring the effectiveness of this new treatment.

Incidental gastrointestinal 18F-Fluorodeoxyglucose uptake associated with lung cancer.

BACKGROUND: F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is increasingly used for the initial staging and restaging of lung cancer. Incidental gastrointestinal findings are often observed on (18)F-FDG PET/CT. The objective of this study was to assess incidental 18F-FDG uptake by the gastrointestinal tract (GIT) in patients with lung cancer. METHODS: Two hundred thirty consecutive 18F-FDG PET/CT examinations performed for lung cancer over a 3-year period were retrospectively reviewed for the presence of incidental FDG uptake in the GIT. The charts of patients with positive FDG uptake were then reviewed and analysed to determine the GIT uptake sites, the standardized uptake value (SUV) max and the final clinical diagnosis. RESULTS: Fifty-two patients (52/230, 23%) demonstrated incidental FDG uptake in the GIT. Thirty-three patients (63.5%) had diffuse uptake (oesophagus, n = 2, colon, n = 31) and 19 patients (36.5%) had focal uptake (oesophagus, n = 1, small bowel, n = 1, ascending colon, n = 5, descending colon, n = 4, sigmoid, n = 4, rectum, n = 3, and anal margin, n = 1). Twelve of the 52 patients with GIT uptake were further investigated, revealing, a diagnosis of malignancy in 4 patients with focal FDG uptake. No significant differences in mean SUVmax were observed between patients with malignant and benign GIT diseases. CONCLUSION: This study demonstrates a high incidence of FDG uptake in the GIT associated with lung cancer. Focal GIT uptake was frequently associated with malignant disease. These results suggest that further GIT investigations should be performed in patients with focal GIT uptake.

Prognostic value of (18)F-FDG PET/CT metabolic parameters in metastatic differentiated thyroid cancers.

PURPOSE: To evaluate the prognostic value of F-fluorodeoxyglucose positron emission tomography (FDG PET) with quantitative analysis using metabolic parameters in metastatic differentiated thyroid cancer (DTC). MATERIALS AND METHODS: The FDG-PET scans of 37 patients with metastatic DTC were studied retrospectively. The number of FDG-avid lesions, the SUVmax, the SULpeak of the lesion with the highest FDG uptake, the overall metabolic tumor volume (MTV), and the total lesion glycolysis (TLG) were measured. Curves of progression-free survival (Kaplan-Meier) and Cox univariate and multivariate analyses determined the prognostic factors for survival. RESULTS: Progression-free survival was better in patients with less than 10 FDG-avid lesions (P = 0.0089), the SUVmax less than 10 (P = 0.0026), the SULpeak less than 5 (P = 0.0004), and the TLG less than 154 (P = 0.0110).Cox analyses showed that only the result of the PET scan was predictive of survival (age, TNM stage, histology, and the I whole body radioiodine scan were not associated with prognosis). In the univariate analysis, prognostic factors for progression-free survival and overall survival were the SUVmax (P = 0.004; P = 0.018), the SULpeak (P = 0.001; P = 0.017), and the TLG (P = 0.014; P = 0.012). The number of FDG-avid lesions was significantly associated with progression-free survival (P = 0.012), but not the MTV. In the multivariate analysis, the number of FDG-avid lesions and the SULpeak were independent prognostic factors. CONCLUSIONS: FDG PET using metabolic parameters is a prognostic factor in metastatic DTC. It could improve the therapeutic management and follow-up of patients.

Cognitive impairment in systemic lupus erythematosus women with elevated autoantibodies and normal single photon emission computerized tomography.

BACKGROUND: Systemic lupus erythematosus (SLE) is known to induce psychiatric disorders, from psychoses to maladaptive coping. Brain autoantibodies were proposed to explain SLE neuropsychiatric disorders and found to be elevated before the onset of clinical symptoms. We assessed cognition in Caucasian SLE women with elevated autoantibodies without overt neuropsychiatric syndromes, in conjunction with single photon emission computerized tomography (SPECT). METHODS: 31 women meeting SLE criteria of the American College of Rheumatology (ACR) were included. Patients who met the ACR neuropsychiatric definition were excluded. Matched controls were 23 healthy women from the Champagne-Ardenne region, France. Participants completed neuropsychological and autoantibodies measurements, and 19 completed SPECT. RESULTS: 61% (19/31) of women with SLE and 53% (9/17) of those with normal SPECT had significant global cognitive impairment defined as 4 T-scores <40 in cognitive tests, compared to 0% (0/23) of controls. SLE women also had significantly greater cognitive dysfunction (mean T-score) on the Wechsler Adult Intelligence Scale (WAIS) visual backspan, Trail Making Test A and B, WAIS Digit Symbol Substitution Test and Stroop Interference, compared to controls. Elevated antinuclear antibody correlated with impairment in the WAIS visual span, WAIS visual backspan, and cancellation task; elevated anti-double-stranded DNA antibody and anticardiolipin correlated respectively with impairment in the Trail Making Test A and WAIS auditive backspan. Two SLE women had abnormal SPECT. CONCLUSIONS: A high prevalence of cognitive deficits was found in Caucasian SLE women compared to normal women, which included impairment in cognitive domains important for daily activities. Elevated autoantibodies tended to correlate with cognitive dysfunction.