PET/CT of cranial arteries for a sensitive diagnosis of giant cell arteritis.

OBJECTIVES: To investigate the performance of cranial PET/CT for the diagnosis of GCA. METHODS: All patients with a suspected diagnosis of GCA were prospectively enrolled in this study and had a digital PET/CT with evaluation of cranial arteries if they had not started glucocorticoids >72 h previously. The diagnosis of GCA was retained after at least 6 months of follow-up if no other diagnosis was considered by the clinician and the patient went into remission after at least 6 consecutive months of treatment. Cranial PET/CT was considered positive if at least one arterial segment showed hypermetabolism similar to or greater than liver uptake. RESULTS: For cranial PET/CT, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) were 73.3%, 97.2%, 91.7% and 89.7%, respectively. For extracranial PET/CT, diagnostic performance was lower (Se = 66.7%, Sp = 80.6%, PPV = 58.8%, NPV = 85.3%). The combination of cranial and extracranial PET/CT improved overall sensitivity (Se = 80%) and NPV (NPV = 90.3%) while decreasing overall specificity (Sp = 77.8%) and PPV (PPV = 60%). CONCLUSION: Cranial PET/CT can be easily combined with extracranial PET/CT with a limited increase in examination time. Combined cranial and extracranial PET/CT showed very high diagnostic accuracy for the diagnosis of GCA. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05246540.

Segmentation of the aorta in systolic phase from 4D flow MRI: multi-atlas vs. deep learning.

OBJECTIVE: In the management of the aortic aneurysm, 4D flow magnetic resonance Imaging provides valuable information for the computation of new biomarkers using computational fluid dynamics (CFD). However, accurate segmentation of the aorta is required. Thus, our objective is to evaluate the performance of two automatic segmentation methods on the calculation of aortic wall pressure. METHODS: Automatic segmentation of the aorta was performed with methods based on deep learning and multi-atlas using the systolic phase in the 4D flow MRI magnitude image of 36 patients. Using mesh morphing, isotopological meshes were generated, and CFD was performed to calculate the aortic wall pressure. Node-to-node comparisons of the pressure results were made to identify the most robust automatic method respect to the pressures obtained with a manually segmented model. RESULTS: Deep learning approach presented the best segmentation performance with a mean Dice similarity coefficient and a mean Hausdorff distance (HD) equal to 0.92+/- 0.02 and 21.02+/- 24.20 mm, respectively. At the global level HD is affected by the performance in the abdominal aorta. Locally, this distance decreases to 9.41+/- 3.45 and 5.82+/- 6.23 for the ascending and descending thoracic aorta, respectively. Moreover, with respect to the pressures from the manual segmentations, the differences in the pressures computed from deep learning were lower than those computed from multi-atlas method. CONCLUSION: To reduce biases in the calculation of aortic wall pressure, accurate segmentation is needed, particularly in regions with high blood flow velocities. Thus, the deep learning segmen-tation method should be preferred.

Acute myocarditis with autoimmune features: one-year follow-up with CMR.

In this prospective study on patients with acute myocarditis (AM), we aimed to describe the new concept of AMAF (AM with autoimmune features) similar to the previously described interstitial pneumonia with autoimmune features (IPAF). IPAF has recently emerged as a new entity, and IPAF patients appear to have fewer episodes of exacerbation and better survival than patients with idiopathic pulmonary fibrosis. Consecutive patients with infarct-like CMR-confirmed AM were classified AMAF if their serologic status measured from blood sampled at presentation was positive (antinuclear antibodies (ANA) ≥ 1:320), but without meeting established classification criteria for connective tissue disease (CTD). The myocardial tissue abnormalities and their progression were assessed on cardiac magnetic resonance (CMR) within 7 days following symptom onset and at 1 year according to their seropositivity. Among the 64 AM patients included, seven presented AMAF (11%). At baseline CMR, patients with AMAF had half as much late gadolinium enhancement (LGE) as seronegative AM patients (4.41% (1.47-4.41) of myocardial volume versus 8.82% (5.88-14.71), p = 0.01, respectively). At 1-year of follow-up, persistent myocardial scarring was less frequent in AMAF patients (n = 2 (28.6%) than seronegative AM patients (n = 38 (66.7%) (p = 0.021). AMAF, diagnosed as seropositive AM without a specific autoimmune disease, is not rare and is associated with less extensive LGE in the acute phase. In addition, AMAF patients had more favorable outcomes on 12-month CMR. Prospective studies are needed to address the clinical significance of this new concept and its long-term cardiovascular impact.

[18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor outcome and limited therapeutic options. Imaging of IPF is limited to high-resolution computed tomography (HRCT) which is often not sufficient for a definite diagnosis and has a limited impact on therapeutic decision and patient management. Hypoxia of the lung is a significant feature of IPF but its role on disease progression remains elusive. Thus, the aim of our study was to evaluate hypoxia imaging with [18F]FMISO as a predictive biomarker of disease progression and therapy efficacy in preclinical models of lung fibrosis in comparison with [18F]FDG. METHODS: Eight-week-old C57/BL6 mice received an intratracheal administration of bleomycin (BLM) at day (D) 0 to initiate lung fibrosis. Mice received pirfenidone (300 mg/kg) or nintedanib (60 mg/kg) by daily gavage from D9 to D23. Mice underwent successive PET/CT imaging at several stages of the disease (baseline, D8/D9, D15/D16, D22/D23) with [18F]FDG and [18F]FMISO. Histological determination of the lung expression of HIF-1α and GLUT-1 was performed at D23. RESULTS: We demonstrate that mean lung density on CT as well as [18F]FDG and [18F]FMISO uptakes are upregulated in established lung fibrosis (1.4-, 2.6- and 3.2-fold increase respectively). At early stages, lung areas with [18F]FMISO uptake are still appearing normal on CT scans and correspond to areas which will deteriorate towards fibrotic lesions at later timepoints. Nintedanib and pirfenidone dramatically and rapidly decreased mean lung density on CT as well as [18F]FDG and [18F]FMISO lung uptakes (pirfenidone: 1.2-, 2.9- and 2.6-fold decrease; nintedanib: 1.2-, 2.3- and 2.5-fold decrease respectively). Early [18F]FMISO lung uptake was correlated with aggressive disease progression and better nintedanib efficacy. CONCLUSION: [18F]FMISO PET imaging is a promising tool to early detect and monitor lung fibrosis progression and therapy efficacy.

Detection of Myocardial Infarction by Cardiac Magnetic Resonance in Embolic Stroke Related to First Diagnosed Atrial Fibrillation.

INTRODUCTION: Elevated troponin levels are found in a significant number of patients who are diagnosed with acute embolic stroke (AES) after first diagnosed atrial fibrillation (AF). These myocardial injuries, which are known as cardiocerebral infarction (CCI), are potentially caused by coronary embolism and correspond to simultaneous cardiac and cerebral embolisms. However, this severe condition remains poorly understood. In this prospective study, we aimed to investigate the prevalence and the cardiac magnetic resonance (CMR) characteristics of CCI. MATERIALS AND METHODS: Consecutive patients with first diagnosed AF hospitalized for AES in a neurovascular intensive care unit from 2019 to 2020 were included. Troponin Ic kinetic were measured <72 h, MRI and coronary angiography or CT scan were performed <7 days after admission. Patients with significant coronary lesions were excluded. RESULTS: During the study period, 1150 patients with strokes were hospitalized in the neurovascular intensive care unit (ICU). Of these patients, 955 had an ischemic stroke and 97 had a transient ischemic attack. Among the 44 patients with AES and with first diagnosed AF, 34 patients underwent CMR and CMR analysis identified 12 MI. A significant rise in troponin (>0.10 µg/L) was observed in 35% of the total population (12/34 patients). More specifically, a rise was seen in 23% of the AES without MI group, 58% of the AES with MI. In addition, coronary embolism was identified in 3 patients who underwent coronary angiography (3/12) and MI was often (30%) localized in infero-latero-medial and infero-apical segments. Most AES were localized in the superficial sylvian territory. CONCLUSION: We found a high prevalence of CMR-confirmed double embolization sites in the acute phase of an embolic stroke. Further studies are required to better characterize the pathophysiology, clinical course and prognostic value of CCI. Moreover, optimal management strategies, including antiplatelet therapy, remain to be determined.

Subtype-Guided 18 F-FDG PET/CT in Tailoring Axillary Surgery Among Patients with Node-Positive Breast Cancer Treated with Neoadjuvant Chemotherapy: A Feasibility Study.

BACKGROUND: The purpose of this study was to investigate the value of 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) in tailoring axillary surgery by predicting nodal response among patients with node-positive breast cancer after neoadjuvant chemotherapy (NAC). METHODS: One hundred thirty-three patients with breast cancer with biopsy-confirmed nodal metastasis were prospectively enrolled. 18 F-FDG PET/CT scan was performed before NAC (a second one after two cycles with baseline maximum standardized uptake value [SUVmax ] ≥2.5), and a subset of patients underwent targeted axillary dissection (TAD). All the patients underwent axillary lymph node dissection (ALND). The accuracy was calculated by a comparison with the final pathologic results. RESULTS: With the cutoff value of 2.5 for baseline SUVmax and 78.4% for change in SUVmax , sequential 18 F-FDG PET/CT scans demonstrated a sensitivity of 79.0% and specificity of 71.4% in predicting axillary pathologic complete response with an area under curve (AUC) of 0.75 (95% confidence interval, 0.65-0.84). Explorative subgroup analyses indicated little value for estrogen receptor (ER)-negative, human epidermal growth factor receptor 2 (HER2)-positive patients (AUC, 0.55; sensitivity, 56.5%; specificity, 50.0%). Application of 18 F-FDG PET/CT could spare 19 patients from supplementary ALNDs and reduce one of three false-negative cases in TAD among the remaining patients without ER-negative/HER2-positive subtype. CONCLUSION: Application of the subtype-guided 18 F-FDG PET/CT could accurately predict nodal response and aid in tailoring axillary surgery among patients with node-positive breast cancer after NAC, which includes identifying candidates appropriate for TAD or directly proceeding to ALND. This approach might help to avoid false-negative events in TAD. IMPLICATIONS FOR PRACTICE: This feasibility study showed that 18 [F]-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) could accurately predict nodal response after neoadjuvant chemotherapy (NAC) among patients with breast cancer with initial nodal metastasis except in estrogen receptor-negative, human epidermal growth factor receptor 2-positive subtype. Furthermore, the incorporation of 18 F-FDG PET/CT can tailor subsequent axillary surgery by identifying patients with residual nodal disease, thus sparing those patients supplementary axillary lymph node dissection. Finally, we have proposed a possibly feasible flowchart involving 18 F-FDG PET/CT that might be applied in post-NAC axillary evaluation.

Biological correlates of tumor perfusion and its heterogeneity in newly diagnosed breast cancer using dynamic first-pass 18F-FDG PET/CT.

PURPOSE: The aim of this prospective study is to analyze the global tumor blood flow (BF) and its heterogeneity in newly diagnosed breast cancer (BC) according to tumor biological characteristics and molecular subtypes. These perfusion parameters were compared to those classically derived from metabolic studies to investigate links between perfusion and metabolism. METHODS: Two hundred seventeen newly diagnosed BC patients underwent a 18F-FDG PET/CT exam before any treatment. A 2-min dynamic acquisition, centered on the chest, was performed immediately after intravenous injection of 3 MBq/kg of 18F-FDG, followed by a two-step static acquisition 90 min later. Tumor BF was calculated (in ml/min/g) using a single compartment kinetic model. In addition to standard PET parameters, texture features (TF) describing the heterogeneity of tumor perfusion and metabolism were extracted. Patients were divided into three groups: Luminal (HR+/HER2-), HER2 (HER2+), and TN (HR-/HER2-). Global and TF parameters of BF and metabolism were compared in different groups of patients according to tumor biological characteristics. RESULTS: Tumors with lymph node involvement showed a higher perfusion, whereas no significant differences in SUV_max or SUV_mean were reported. TN tumors had a higher metabolic activity than HER2 and luminal tumors but no significant differences in global BF values were noted. HER2 tumors exhibited a larger tumor heterogeneity of both perfusion and metabolism compared to luminal and TN tumors. Heterogeneity of perfusion appeared well correlated to that of metabolism. CONCLUSIONS: The study of breast cancer perfusion shows a higher BF in large tumors and in tumors with lymph node involvement, not paralleled by similar modifications in tumor global metabolism. In addition, the observed correlation between the perfusion heterogeneity and the metabolism heterogeneity suggests that tumor perfusion and consequently the process of tumor angiogenesis might be involved in the metabolism heterogeneity previously shown in BC.

Impact of ascending aorta replacement by graft on elastic properties of descending thoracic aorta evaluated by cardiac magnetic resonance imaging.

OBJECTIVE: The aim of our study was to evaluate the impact of aortic root replacement by graft on the elastic properties of the descending thoracic aorta using cardiac magnetic resonance imaging (MRI) and automatic post-processing. MATERIALS AND METHODS: Nineteen patients were operated for an aortic root aneurysm. Cardiac MRI was performed before and after surgery to measure aortic compliance. Images were acquired on a 1.5 T MRI with a conventional aortic MRI protocol plus one additional kinetic sequence orientated perpendicularly to the aorta at the level of pulmonary trunk. The contours of the ascending and descending aortas were detected automatically for each phase with homemade software. RESULTS: Mean time between surgical procedure and earliest post-operative MRI was 18.2 ± 7.1 months. There was no significant difference between the pre- and earliest post-operative mean descending aorta areas and no significant modification in descending aortic compliance after aortic root replacement (1.43 ± 0.84 vs 1.37 ± 0.58 mm2/mmHg, p = 0.47). Pre- and post-operative systolic and diastolic blood pressure were similar. There was a significant decrease in ascending aortic compliance after surgery (2.52 ± 1.24 vs 0.91 ± 0.52 mm2/mmHg; p < 0.0001). DISCUSSION: The aortic root replacement by graft was not associated with changes in elastic properties of the descending aorta at short term. CLINICAL REGISTRATION NUMBER: NCT03817008.

Salvage extended field or involved field nodal irradiation in 18F-fluorocholine PET/CT oligorecurrent nodal failures from prostate cancer.

PURPOSE: The concept of metastasis-directed therapy for nodal oligorecurrences with stereotactic body radiotherapy is increasingly accepted. Hence, the comparison between salvage extended field radiotherapy (s-EFRT) and salvage involved field radiotherapy (s-IFRT) in patients with 18F-fluorocholine (FCH) PET/CT+ nodal oligorecurrences from prostate cancer is worthy of investigation. METHODS: Patients with oligorecurrent nodes on FCH PET/CT treated with salvage radiotherapy between 2009 and 2017 in a single tertiary cancer centre were selected for this study. Patients treated with s-IFRT were compared with those treated with s-EFRT. Toxicities and times to failure (TTF) were compared between the two groups. RESULTS: The study included 62 patients with positive lymph nodes only who underwent FCH PET/CT for a rising PSA level after radical prostatectomy or radiotherapy. Of these patients, 35 had s-IFRT and 27 had s-EFRT. After a median follow-up of 41.8 months (range 5.9-108.1 months), no differences were observed in acute or late gastrointestinal and genitourinary toxicities of grade 2 or more between the two groups. The 3-year failure rates were 55.3% (95% CI 37.0-70.3%) in the s-IFRT group and 88.3% (95% CI 66.9-96.1%) in the s-EFRT group (p = 0.0094). In multivariate analysis of TTF, an interval of >5 years was significantly correlated with better outcomes (HR = 0.33, 95% CI 0.13-0.86, p = 0.023). There was a strong trend toward better outcomes with s-EFRT even after adjusting for concomitant androgen-deprivation therapy (HR = 0.38, 95% CI 0.12-1.27, p = 0.116). CONCLUSION: FCH PET-positive node-targeted s-EFRT is feasible with low rates of toxicity and longer TTF, suggesting that oligorecurrent nodal disease diagnosed on FCH PET is unlikely.

SUV calculation in breast cancer: which normalization should be applied when using 18F-FDG PET?

BACKGROUND: When using 18F-FDG PET, glucose metabolism quantification is affected by various factors. We aimed to investigate the benefit of different standardized uptake value (SUV) normalizations to improve the accuracy of 18F-FDG uptake to predict breast cancer aggressiveness and response to treatment. METHODS: Two hundred fifty-two women with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC) were included. Women underwent 18F-FDG PET before and after the first course of NAC. Glucose serum levels, patient heights and weights were recorded at the time of each PET exam. Four different procedures for SUV normalization of the primary tumor were used: by body weight (SUVBW) by blood glucose level (SUVG), by lean body mass (SUL) and then corrected for both lean body mass and blood glucose level (SULG). RESULTS: At baseline, SUL was significantly lower than SUVBW (5.9±4.0 and 9.5±6.5, respectively; P<0.0001), whereas SUVG and SUVBW were not significantly different (9.7±6.4 and 9.5±6.5, respectively; P=0.67). Concerning SUV changes (ΔSUV), the different normalizations methods did not induce significant quantitative differences. The correlation coefficients were high between the four normalizations methods of SUV1, SUV2 and ΔSUVB (R>0.95; P<0.0001). High baseline SUVBW measures were positively correlated with the biological tumor characteristics of aggressiveness and proliferation (P<0.001): ductal carcinoma, high tumor grading, high mitotic activity, negative estrogen receptor status and the TNBC subtype. ΔSUVBW was highly predictive of pCR (AUC=0.76 on ROC curve analysis; P<0.0001). The different SUV normalizations yields identical statistical results and AUC to predict tumor biological aggressiveness and response to therapy. CONCLUSIONS: In the present setting, SUVBW and SUL can be considered as robust measures and be used in future multicenter trials. The additional normalization of SUV by glycemia involves stringent methodologic procedures to avoid biased risk measurements and offers no statistical advantages.

Role of positron emission tomography for the monitoring of response to therapy in breast cancer.

This review considers the potential utility of positron emission tomography (PET) tracers in the setting of response monitoring in breast cancer, with a special emphasis on glucose metabolic changes assessed with (18)F-fluorodeoxyglucose (FDG). In the neoadjuvant setting of breast cancer, the metabolic response can predict the final complete pathologic response after the first cycles of chemotherapy. Because tumor metabolic behavior highly depends on cancer subtype, studies are ongoing to define the optimal metabolic criteria of tumor response in each subtype. The recent multicentric randomized AVATAXHER trial has suggested, in the human epidermal growth factor 2-positive subtype, a clinical benefit of early tailoring the neoadjuvant treatment in women with poor metabolic response after the first course of treatment. In the bone-dominant metastatic setting, there is increasing clinical evidence that FDG-PET/computed tomography (CT) is the most accurate imaging modality for assessment of the tumor response to treatment when both metabolic information and morphologic information are considered. Nevertheless, there is a need to define standardized metabolic criteria of response, including the heterogeneity of response among metastases, and to evaluate the costs and health outcome of FDG-PET/CT compared with conventional imaging. New non-FDG radiotracers highlighting specific molecular hallmarks of breast cancer cells have recently emerged in preclinical and clinical studies. These biomarkers can take into account the heterogeneity of tumor biology in metastatic lesions. They may provide valuable clinical information for physicians to select and monitor the effectiveness of novel therapeutics targeting the same molecular pathways of breast tumor.

¹8F-FDG PET/CT provides powerful prognostic stratification in the primary staging of large breast cancer when compared with conventional explorations.

PURPOSE: The objective of this study was to assess the impact on management and the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for initial staging of newly diagnosed large breast cancer (BC) when compared with conventional staging. METHODS: We prospectively included 142 patients with newly diagnosed BC and at least grade T2 tumour. All patients were evaluated with complete conventional imaging (CI) procedures (mammogram and/or breast ultrasound, bone scan, abdominal ultrasound and/or CT, X-rays and/or CT of the chest), followed by FDG PET/CT exploration, prior to treatment. The treatment plan based on CI staging was compared with that based on PET/CT findings. CI and PET/CT findings were confirmed by imaging and clinical follow-up and/or pathology when assessable. Progression-free survival (PFS) was analysed using the Cox proportional hazards regression model. RESULTS: According to CI staging, 79 patients (56%) were stage II, 46 (32%) stage III and 17 (12%) stage IV (distant metastases). Of the patients, 30 (21%) were upstaged by PET/CT, including 12 (8%) from stage II or III to stage IV. On the other hand, 23 patients (16%) were downstaged by PET/CT, including 4 (3%) from stage IV to stage II or III. PET/CT had a high or medium impact on management planning for 18 patients (13%). Median follow-up was 30 months (range 9-59 months); 37 patients (26%) experienced recurrence or progression of disease during follow-up and 17 patients (12%) died. The Cox model indicated that CI staging was significantly associated with PFS (p = 0.01), but PET/CT staging provided stronger prognostic stratification (p < 0.0001). Moreover, Cox regression multivariate analysis showed that only PET/CT staging remained associated with PFS (p < 0.0001). CONCLUSION: FDG PET/CT provides staging information that more accurately stratifies prognostic risk in newly diagnosed large BC when compared with conventional explorations alone.

Baseline metabolic tumour volume is an independent prognostic factor in Hodgkin lymphoma.

PURPOSE: The presence of a bulky tumour at staging in Hodgkin lymphoma (HL) is a predictor of a poor outcome. The total metabolic tumour volume at baseline (TMTV0) computed on PET may improve the evaluation of tumour burden. To explore the clinical usefulness of TMTV0, we compared the prognostic value of TMTV0, tumour bulk and interim PET response in a retrospective single-centre study. METHODS: From 2007 to 2010, 59 consecutive patients with a first diagnosis of HL were treated in our institution. PET was done at baseline (PET0) and after two cycles of chemotherapy (PET2), and treatment was not modified according to the PET2 result. TMTV0 was measured with a semiautomatic method using a 41 % SUVmax threshold. SUVmax reduction between PET0 and PET2 (ΔSUVmaxPET0-2) was also computed. Based on ROC analysis, patients with a ΔSUVmaxPET0-2 >71 % were considered good responders and a TMTV0 >225 ml was considered to represent hypermetabolic bulky disease. RESULTS: Median TMTV0 was 117 ml and 17 patients (29 %) had a TMTV0 >225 ml. TMTV0 (>225 ml vs. ≤225 ml) and tumour bulk (<10 cm vs. ≥10 cm) were predictive of 4-year PFS: 42 % vs. 85 % (p = 0.001) and 44 % vs. 79 % (p < 0.03), respectively. In multivariate analysis, using ΔSUVmaxPET0-2, TMTV0 and bulky tumour as covariates, only ΔSUVmaxPET0-2 (p = 0.0005, RR 6.3) and TMTV0 (p < 0.006, RR 4.4) remained independent predictors of PFS. Three prognosis groups were thus identified: ΔSUVmaxPET0-2 >71 % and TMTV0 ≤225 ml (n = 37, 63 %), ΔSUVmaxPET0-2 = <71 % or TMTV0 >225 ml (n = 17, 29 %), and ΔSUVmaxPET0-2 = <71 % and TMTV0 >225 ml (n = 5, 8 %). In these three groups the 4-year PFS rates were 92 %, 49 %, and 20 % (p < 0.0001), respectively. CONCLUSION: TMTV0 is more relevant than tumour bulk for predicting the outcome in patients with HL, and adds a significant prognostic insight to interim PET response assessment. The combination of TMTV0 and ΔSUVmaxPET0-2 made it possible to identify three subsets of HL patients with different outcomes. This may guide clinicians in their choice of therapeutic strategy.

Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using (18)F-FDG PET in luminal HER2-negative breast cancer.

PURPOSE: The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC). METHODS: This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (∆SUV) was calculated. RESULTS: Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p = 0.017) and higher grade (p = 0.04). The median follow-up period was 64.2 months (range 11.5-93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR) = 6.52, p = 0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV < 16%, HR = 10.63, p = 0.004). Five-year overall survival in these poor responder patients was 49.2%. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15%, respectively. CONCLUSION: In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients' survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response.

HER2-positive breast cancer: ¹8F-FDG PET for early prediction of response to trastuzumab plus taxane-based neoadjuvant chemotherapy.

PURPOSE: To investigate the value of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET/CT) to predict a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. MATERIAL AND METHODS: Fifty-seven consecutive women with HER2-positive breast cancer, treated with trastuzumab plus taxane-based NAC, were prospectively included. Maximum Standardized Uptake Value of the primary tumor and axillary nodes were measured at baseline (PET1.SUVmax) and after the first course of NAC (PET2.SUVmax). Tumor metabolic volumes were assessed to determine Total Lesion Glycolysis (TLG). The tumor metabolic response (ΔSUVmax and ΔTLG) was calculated. RESULTS: In univariate analysis, negative hormonal receptor status (p = 0.04), high tumor grade (p = 0.03), and low tumor PET2.SUVmax (p = 0.001) were predictive of pCR. Tumor ΔSUVmax correlated with pCR (p = 0.03), provided that tumors with low metabolic activity at baseline were excluded. ΔTLG did not correlate with pCR. In multivariate analysis, tumor PET2.SUVmax < 2.1 was the best independent predictive factor (Odds ratio =14.3; p = 0.004) with both negative and positive predictive values of 76 %. Although the metabolic features of the primary tumor did not depend on hormonal receptor status, both the baseline metabolism and early response of axillary nodes were higher if estrogen receptors were not expressed (p = 0.01 and p = 0.03, respectively). CONCLUSION: In HER2-positive breast cancer, very low tumor residual metabolism after the first cycle of NAC (SUVmax < 2.1) was the main predictor of pCR. These results should be further explored in multicenter studies and incorporated into the design of clinical trials.

Diagnostic Performances of 18F-Fluorocholine PET/CT as First-Line Functional Imaging Method for Localization of Hyperfunctioning Parathyroid Tissue in Primary Hyperparathyroidism.

RATIONALE AND OBJECTIVES: This study evaluated the diagnostic performance of 18F-fluorocholine (FCH) PET/CT as the first-line functional imaging method for preoperative localization of hyperfunctioning parathyroid glands (HPGs) in patients with primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: This retrospective single-center study included 80 consecutive patients with PHPT, referred for FCH PET/CT between January 2018 and July 2022, and who subsequently underwent surgery. The diagnostic performance of FCH PET/CT was compared to histological results for per-lesion analysis, and to postoperative resolution of biochemical PHPT for per-patient analysis. RESULTS: 18F-FCH-PET/CT revealed 95 positive foci in 77/80 patients and was negative in 3/80 patients. Postoperative resolution of HPT was obtained in 67/80 patients (84%). Per-lesion analysis showed 80 true positives, five true negatives, 11 false negatives, and eight false positives. Seven PET-positive foci could not be compared to histology. In a first per-lesion analysis, excluding these seven anomalies, sensitivity and positive predictive value (PPV) of FCH PET/CT were 88% (95% CI: 79-94) and 91% (95% CI: 87-94), respectively. In a second per-lesion analysis considering the seven anomalies as false positives (maximum bias analysis), PPV was 84% (95% CI: 80%-87%). By per-patient analysis, FCH PET/CT correctly identified and located all pathological glands in 56/80 (70%, 95% CI: 59-80) patients. CONCLUSION: 18F-Fluorocholine PET/CT appears to be an effective pre-surgical imaging method for localization of hyperfunctioning parathyroid tissue in patients with PHPT.

Validation of a discovery MI 4-ring model according to the NEMA NU 2-2018 standards: from Monte Carlo simulations to clinical-like reconstructions.

BACKGROUND: We propose a comprehensive evaluation of a Discovery MI 4-ring (DMI) model, using a Monte Carlo simulator (GATE) and a clinical reconstruction software package (PET toolbox). The following performance characteristics were compared with actual measurements according to NEMA NU 2-2018 guidelines: system sensitivity, count losses and scatter fraction (SF), coincidence time resolution (CTR), spatial resolution (SR), and image quality (IQ). For SR and IQ tests, reconstruction of time-of-flight (TOF) simulated data was performed using the manufacturer's reconstruction software. RESULTS: Simulated prompt, random, true, scatter and noise equivalent count rates closely matched the experimental rates with maximum relative differences of 1.6%, 5.3%, 7.8%, 6.6%, and 16.5%, respectively, in a clinical range of less than 10 kBq/mL. A 3.6% maximum relative difference was found between experimental and simulated sensitivities. The simulated spatial resolution was better than the experimental one. Simulated image quality metrics were relatively close to the experimental results. CONCLUSIONS: The current model is able to reproduce the behaviour of the DMI count rates in the clinical range and generate clinical-like images with a reasonable match in terms of contrast and noise.

Respective contribution of baseline clinical data, tumour metabolism and tumour blood-flow in predicting pCR after neoadjuvant chemotherapy in HER2 and Triple Negative breast cancer.

BACKGROUND: The aim of this study is to investigate the added value of combining tumour blood flow (BF) and metabolism parameters, including texture features, with clinical parameters to predict, at baseline, the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with newly diagnosed breast cancer (BC). METHODS: One hundred and twenty-eight BC patients underwent a 18F-FDG PET/CT before any treatment. Tumour BF and metabolism parameters were extracted from first-pass dynamic and delayed PET images, respectively. Standard and texture features were extracted from BF and metabolic images. Prediction of pCR was performed using logistic regression, random forest and support vector classification algorithms. Models were built using clinical (C), clinical and metabolic (C+M) and clinical, metabolic and tumour BF (C+M+BF) information combined. Algorithms were trained on 80% of the dataset and tested on the remaining 20%. Univariate and multivariate features selections were carried out on the training dataset. A total of 50 shuffle splits were performed. The analysis was carried out on the whole dataset (HER2 and Triple Negative (TN)), and separately in HER2 (N=76) and TN (N=52) tumours. RESULTS: In the whole dataset, the highest classification performances were observed for C+M models, significantly (p-value<0.01) higher than C models and better than C+M+BF models (mean balanced accuracy of 0.66, 0.61, and 0.64 respectively). For HER2 tumours, equal performances were noted for C and C+M models, with performances higher than C+M+BF models (mean balanced accuracy of 0.64, and 0.61 respectively). Regarding TN tumours, the best classification results were reported for C+M models, with better performances than C and C+M+BF models but not significantly (mean balanced accuracy of 0.65, 0.63, and 0.62 respectively). CONCLUSION: Baseline clinical data combined with global and texture tumour metabolism parameters assessed by 18F-FDG PET/CT provide a better prediction of pCR after NAC in patients with BC compared to clinical parameters alone for TN, and HER2 and TN tumours together. In contrast, adding BF parameters to the models did not improve prediction, regardless of the tumour subgroup analysed.

PET digitization chain for Monte Carlo simulation in GATE.

Objective. We introduce a versatile methodology for the accurate modelling of PET imaging systems via Monte Carlo simulations, using the Geant4 application for tomographic emission (GATE) platform. Accurate Monte Carlo modelling involves the incorporation of a complete analytical signal processing chain, called the digitizer in GATE, to emulate the different count rates encountered in actual positron emission tomography (PET) systems.Approach. The proposed approach consists of two steps: (1) modelling the digitizer to replicate the detection chain of real systems, covering all available parameters, whether publicly accessible or supplied by manufacturers; (2) estimating the remaining parameters, i.e. background noise level, detection efficiency, and pile-up, using optimisation techniques based on experimental single and prompt event rates. We show that this two-step optimisation reproduces the other experimental count rates (true, scatter, and random), without the need for additional adjustments. This method has been applied and validated with experimental data derived from the NEMA count losses test for three state-of-the-art SiPM-based time-of-flight (TOF)-PET systems: Philips Vereos, Siemens Biograph Vision 600 and GE Discovery MI 4-ring.Main results. The results show good agreement between experiments and simulations for the three PET systems, with absolute relative discrepancies below 3%, 6%, 6%, 7% and 12% for prompt, random, true, scatter and noise equivalent count rates, respectively, within the 0-10 kBq·ml-1activity concentration range typically observed in whole-body18F scans.Significance. Overall, the proposed digitizer optimisation method was shown to be effective in reproducing count rates and NECR for three of the latest generation SiPM-based TOF-PET imaging systems. The proposed methodology could be applied to other PET scanners.