Publications by authors named "Axel Van Der Gucht"

38 Publications

Macrophagic myofasciitis-associated dysfunctioning: An update of neuropsychological and neuroimaging features.

Best Pract Res Clin Rheumatol 2018 10 24;32(5):640-650. Epub 2019 Apr 24.

INSERM U955-Equipe 10, Université Paris Est-Créteil, 94000 Créteil, France; Centre Expert de Pathologie Neuromusculaire, CHU Henri Mondor (AP-HP), 94000 Créteil, France. Electronic address:

Macrophagic myofasciitis (MMF) syndrome is a subtype of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld's syndrome, characterized by the presence of stereotyped inflammatory lesions at muscle biopsy attesting the long-term persistence of aluminum hydroxide particles at the site of previous immunization. Most frequently reported symptoms are chronic arthromyalgias and fatigue and cognitive complaint. MMF-associated cognitive disorder (MACD) is characterized by the dysfunctioning of attention, executive functions, short-term term and long-term memory, and, in some instances, left ear extinction. MACD is expressed in a chronic, nonevolving, well-defined syndromic framework within which the expression in terms of severity differs from one patient to another. While brain MRI is usually noncontributive, functional imaging using SPECT and PET has revealed the existence of a suggestive pathological pattern with involvement of posterior associative areas, temporal lobes, limbic system, and cerebellum. Put together, neuropsychological and functional neuroimaging investigations support the view that MACD relates to organic central nervous system involvement.
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http://dx.doi.org/10.1016/j.berh.2019.04.003DOI Listing
October 2018

First in-human radiation dosimetry of the gastrin-releasing peptide (GRP) receptor antagonist Ga-NODAGA-MJ9.

EJNMMI Res 2018 Dec 12;8(1):108. Epub 2018 Dec 12.

Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland.

Background: Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast. This study presents the first human dosimetry of Ga-NODAGA-MJ9 in the first five consecutive patients with recurrent prostate cancer included in a dual-tracer positron emission tomography (PET) protocol. Five male patients with biochemical relapse of prostate adenocarcinoma underwent four whole-body time-of-flight PET/CT scans within 2 h after tracer injection. To be used as input in OLINDA/EXM 2.0, time-integrated activity coefficients were derived from manually drawn regions of interest over the following body regions: brain, thyroid, lungs, heart, liver, gallbladder, spleen, stomach, kidneys, adrenals, red marrow, pancreas, intestines, urinary bladder and whole body. Organ absorbed doses and effective dose (ED) were calculated with OLINDA/EXM 2.0 using the NURBS voxelized phantoms adjusted to the ICRP-89 organ masses and ICRP103 tissue-weighting factors. Additional absorbed dose estimations were performed with OLINDA/EXM 1.1 to be comparable with similar previous publications.

Results: The body regions receiving the highest absorbed doses were the pancreas, the urinary bladder wall, the small intestine and the kidneys (260, 69.8, 38.8 and 34.8 μGy/MBq respectively). The ED considering a 30-min urinary voiding cycle was 17.6 μSv/MBq in male patients. The increment of voiding time interval produced a significant increase of absorbed doses in bladder, prostate and testes, as well as an increase of ED. ED also increased if calculated with OLINDA/EXM 1.1. These results have been discussed in view of similar publications on bombesin analogues or on other commonly used theranostic peptides.

Conclusions: The pancreas is the most irradiated organ after the injection of Ga-NODAGA-MJ9, followed by the urinary bladder wall, the small intestine and the kidneys. ED is in the same range of other common Ga-labelled peptides. Differences with similarly published studies on bombesin analogues exist, and are mainly dependent on the methodology used for absorbed dose calculations.

Trial Registration: Clinicaltrial.Gov identifier: NCT02111954 , posted on 11/042014.
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http://dx.doi.org/10.1186/s13550-018-0462-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291411PMC
December 2018

Physiological Whole-Brain Distribution of [F]FDOPA Uptake Index in Relation to Age and Gender: Results from a Voxel-Based Semi-quantitative Analysis.

Mol Imaging Biol 2019 06;21(3):549-557

Department of Nuclear Medicine & Nancyclotep Imaging Platform, CHRU Nancy, Lorraine University, Nancy, France.

Purpose: 6-[F]fluoro-L-DOPA ([F]FDOPA), a positron emission tomography (PET) amino-acid tracer of brain decarboxylase activity, is used to assess the brain dopaminergic system. Using a voxel-based semi-quantitative analysis, this study aimed to determine whether a current brain uptake index of [F]FDOPA, expressed relative to the occipital background level, varies according to age and gender.

Procedures: One hundred and seventy-seven subjects were retrospectively included. A whole-brain statistical parametric mapping analysis of the [F]FDOPA uptake index in parametric PET images was performed at a voxel threshold of p < 0.05 (corrected) and p < 0.005 (uncorrected, k cluster > 125).

Results: Striatal uptake indices were influenced by age, negatively for the caudate nucleus and positively for the putamen, as well as by gender, with a lower left putaminal uptake index in women. Extra-striatal uptake indices were influenced by age, negatively for the frontal cortex and brainstem and positively for the occipital cortex and cerebellum, as well as by gender (diffuse increase in women).

Conclusions: The uptake index of [F]FDOPA exhibited significant physiological variations according to age and gender and should therefore be considered for PET interpretation.
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http://dx.doi.org/10.1007/s11307-018-1256-1DOI Listing
June 2019

Voxel-based 18F-FET PET segmentation and automatic clustering of tumor voxels: A significant association with IDH1 mutation status and survival in patients with gliomas.

PLoS One 2018 28;13(6):e0199379. Epub 2018 Jun 28.

Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland.

Introduction: Aim was to develop a full automatic clustering approach of the time-activity curves (TAC) from dynamic 18F-FET PET and evaluate its association with IDH1 mutation status and survival in patients with gliomas.

Methods: Thirty-seven patients (mean age: 45±13 y) with newly diagnosed gliomas and dynamic 18F-FET PET before any histopathologic investigation or treatment were retrospectively included. Each dynamic 18F-FET PET was realigned to the first image and spatially normalized in the Montreal Neurological Institute template. A tumor mask was semi-automatically generated from Z-score maps. Each brain tumor voxel was clustered in one of the 3 following centroids using dynamic time warping and k-means clustering (centroid #1: slowly increasing slope; centroid #2: rapidly increasing followed by slowly decreasing slope; and centroid #3: rapidly increasing followed by rapidly decreasing slope). The percentage of each dynamic 18F-FET TAC within tumors and other conventional 18F-FET PET parameters (maximum and mean tumor-to-brain ratios [TBRmax and TBRmean], time-to-peak [TTP] and slope) was compared between wild-type and IDH1 mutant tumors. Their prognostic value was assessed in terms of progression free-survival (PFS) and overall survival (OS) by Kaplan-Meier estimates.

Results: Twenty patients were IDH1 wild-type and 17 IDH1 mutant. Higher percentage of centroid #1 and centroid #3 within tumors were positively (P = 0.016) and negatively (P = 0.01) correlated with IDH1 mutated status. Also, TBRmax, TBRmean, TTP, and slope discriminated significantly between tumors with and without IDH1 mutation (P range 0.01 to 0.04). Progression occurred in 22 patients (59%) at a median of 13.1 months (7.6-37.6 months) and 13 patients (35%) died from tumor progression. Patients with a percentage of centroid #1 > 90% had a longer survival compared with those with a percentage of centroid #1 < 90% (P = 0.003 for PFS and P = 0.028 for OS). This remained significant after stratification on IDH1 mutation status (P = 0.029 for PFS and P = 0.034 for OS). Compared to other conventional 18F-FET PET parameters, TTP and slope were associated with PFS and OS (P range 0.009 to 0.04).

Conclusions: Based on dynamic 18F-FET PET acquisition, we developed a full automatic clustering approach of TAC which appears to be a valuable noninvasive diagnostic and prognostic marker in patients with gliomas.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199379PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023198PMC
April 2019

Intramuscular Follicular Lymphoma.

Clin Nucl Med 2018 Sep;43(9):682-684

Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland.

We present an interesting image of a painless growing mass of the right arm in a 76-year-old man. A musculoskeletal MRI of the right arm showed a 7.5 × 3-cm homogeneous, well-defined mass, elongated along the course of muscle fascias and independent of the adjacent bone. A core-needle biopsy was performed, and the diagnosis of low-grade follicular lymphoma was established. Intramuscular lymphoma should be integrated into the differential diagnosis of tumors surrounding neurovascular structures, alongside peripheral nerve tumors and soft tissue sarcoma. MRI and whole-body F-FDG PET/CT features provided useful information to refine differential diagnosis in this case.
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http://dx.doi.org/10.1097/RLU.0000000000002180DOI Listing
September 2018

Automatic lesion detection and segmentation of 18F-FET PET in gliomas: A full 3D U-Net convolutional neural network study.

PLoS One 2018 13;13(4):e0195798. Epub 2018 Apr 13.

Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland.

Introduction: Amino-acids positron emission tomography (PET) is increasingly used in the diagnostic workup of patients with gliomas, including differential diagnosis, evaluation of tumor extension, treatment planning and follow-up. Recently, progresses of computer vision and machine learning have been translated for medical imaging. Aim was to demonstrate the feasibility of an automated 18F-fluoro-ethyl-tyrosine (18F-FET) PET lesion detection and segmentation relying on a full 3D U-Net Convolutional Neural Network (CNN).

Methods: All dynamic 18F-FET PET brain image volumes were temporally realigned to the first dynamic acquisition, coregistered and spatially normalized onto the Montreal Neurological Institute template. Ground truth segmentations were obtained using manual delineation and thresholding (1.3 x background). The volumetric CNN was implemented based on a modified Keras implementation of a U-Net library with 3 layers for the encoding and decoding paths. Dice similarity coefficient (DSC) was used as an accuracy measure of segmentation.

Results: Thirty-seven patients were included (26 [70%] in the training set and 11 [30%] in the validation set). All 11 lesions were accurately detected with no false positive, resulting in a sensitivity and a specificity for the detection at the tumor level of 100%. After 150 epochs, DSC reached 0.7924 in the training set and 0.7911 in the validation set. After morphological dilatation and fixed thresholding of the predicted U-Net mask a substantial improvement of the DSC to 0.8231 (+ 4.1%) was noted. At the voxel level, this segmentation led to a 0.88 sensitivity [95% CI, 87.1 to, 88.2%] a 0.99 specificity [99.9 to 99.9%], a 0.78 positive predictive value: [76.9 to 78.3%], and a 0.99 negative predictive value [99.9 to 99.9%].

Conclusions: With relatively high performance, it was proposed the first full 3D automated procedure for segmentation of 18F-FET PET brain images of patients with different gliomas using a U-Net CNN architecture.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195798PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898737PMC
July 2018

Total metabolic tumor volume, circulating tumor cells, cell-free DNA: distinct prognostic value in follicular lymphoma.

Blood Adv 2018 04;2(7):807-816

Paris-Est Créteil University, Créteil, France.

Outcomes for follicular lymphoma (FL) have greatly improved, but most patients will ultimately relapse. High total metabolic tumor volume (TMTV), computed from baseline F-fluorodeoxyglucose-positron emission tomography (PET), is associated with shorter progression-free survival (PFS), but circulating tumor cells (CTCs) and cell-free DNA (cfDNA) may also reflect tumor burden and be of prognostic value. The aim of our study was to correlate CTCs and cfDNA with TMTV in FL at diagnosis and to determine their prognostic values. We retrospectively analyzed 133 patients (with previously untreated FL and a baseline PET) from 2 cohorts with either a baseline plasma sample (n = 61) or a bcl2-JH-informative peripheral blood (PB) sample (n = 68). Quantification of circulating bcl2-JH cells and cfDNA was performed by droplet digital polymerase chain reaction. A significant correlation was found between TMTV and both CTCs ( < .0001) and cfDNA ( < .0001). With a median 48-month follow-up, 4-year PFS was lower in patients with TMTV > 510 cm ( = .0004), CTCs >0.0018 PB cells ( = .03), or cfDNA >2550 equivalent-genome/mL ( = .04). In comparison with TMTV alone, no additional prognostic information was obtained by measuring CTCs. In contrast, Cox multivariate analysis, including cfDNA and TMTV, showed that both cfDNA and TMTV remained predictive of outcome. In conclusion, CTCs and cfDNA correlate with TMTV in FL, and all 3 influence patient outcome. PFS was shorter for patients with high cfDNA and TMTV, suggesting that these parameters provide relevant information for tumor-tailored therapy.
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http://dx.doi.org/10.1182/bloodadvances.2017015164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894260PMC
April 2018

Signature of survival: a F-FDG PET based whole-liver radiomic analysis predicts survival after Y-TARE for hepatocellular carcinoma.

Oncotarget 2018 Jan 19;9(4):4549-4558. Epub 2017 Dec 19.

Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland.

Purpose: To generate a predictive whole-liver radiomics scoring system for progression-free survival (PFS) and overall survival (OS) in patients undergoing transarterial radioembolization using Yttrium-90 (Y-TARE) for unresectable hepatocellular carcinoma (uHCC).

Results: The generated pPET-RadScores were significantly correlated with survival for PFS (median of 11.4 mo [95% confidence interval CI: 6.3-16.5 mo] in low-risk group [PFS-pPET-RadScore < 0.09] vs. 4.0 mo [95% CI: 2.3-5.7 mo] in high-risk group [PFS-pPET-RadScore > 0.09]; = 0.0004) and OS (median of 20.3 mo [95% CI: 5.7-35 mo] in low-risk group [OS-pPET-RadScore < 0.11] vs. 7.7 mo [95% CI: 6.0-9.5 mo] in high-risk group [OS-pPET-RadScore > 0.11]; = 0.007). The multivariate analysis confirmed PFS-pPET-RadScore ( = 0.006) and OS-pPET-RadScore ( = 0.001) as independent negative predictors.

Conclusion: Pretreatment F-FDG PET whole-liver radiomics signature appears as an independent negative predictor for PFS and OS in patients undergoing Y-TARE for uHCC.

Methods: Pretreatment F-FDG PET of 47 consecutive patients undergoing Y-TARE for uHCC (31 resin spheres, 16 glass spheres) were retrospectively analyzed. For each patient, based on PET radiomics signature from whole-liver semi-automatic segmentation, PFS and OS predictive PET-radiomics scores (pPET-RadScores) were obtained using LASSO Cox regression. Using X-tile software, the optimal score to predict PFS (PFS-pPET-RadScore) and OS (OS-pPET-RadScore) served as cutoff to separate high and low-risk patients. Survival curves were estimated using the Kaplan-Meier method. The prognostic value of PFS and OS-pPET-RadScore, Barcelona-Clinic Liver Cancer staging system and serum alpha-fetoprotein level was analyzed to predict PFS and OS in multivariate analysis.
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http://dx.doi.org/10.18632/oncotarget.23423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796994PMC
January 2018

Testicular Estrogen-Secreting Leydig Cell Tumor in 18F-FDG PET/CT: An Incidental Detection in a Patient Treated by Chemotherapy for Hodgkin Lymphoma.

Clin Nucl Med 2018 Jan;43(1):41-43

We present images of a 50-year-old man who referred for treatment of a classic Hodgkin lymphoma. While F-FDG PET/CT demonstrated a complete metabolic remission after chemotherapy, an increased F-FDG uptake of a right testicular lesion in F-FDG PET/CT and an unexplained bilateral gynecomastia were observed. A benign Leydig cell tumor was histopathologically proved after a right radical orchiectomy. The serum estradiol level was abnormally elevated reflecting the estrogen-secreting profile. This report highlights that a focal F-FDG uptake in the testicular region with unexplained gynecomastia should suggest the diagnosis of an estrogen-secreting Leydig cell tumor on F-FDG PET/CT.
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http://dx.doi.org/10.1097/RLU.0000000000001905DOI Listing
January 2018

Evaluation of factors influencing F-FET uptake in the brain.

Neuroimage Clin 2018 8;17:491-497. Epub 2017 Nov 8.

Institute of Neuroscience and Medicine (INM-1, -3, -4, -7), Forschungszentrum Jülich, Jülich, Germany; Department of Nuclear Medicine, RWTH Aachen University Hospital, Aachen, Germany; Section JARA-Brain, Jülich-Aachen Research Alliance (JARA), Jülich, Germany.

PET using the amino-acid O-(2-F-fluoroethyl)-l-tyrosine (F-FET) is gaining increasing interest for brain tumour management. Semi-quantitative analysis of tracer uptake in brain tumours is based on the standardized uptake value (SUV) and the tumour-to-brain ratio (TBR). The aim of this study was to explore physiological factors that might influence the relationship of SUV of F-FET uptake in various brain areas, and thus affect quantification of F-FET uptake in brain tumours. Negative F-FET PET scans of 107 subjects, showing an inconspicuous brain distribution of F-FET, were evaluated retrospectively. Whole-brain quantitative analysis with Statistical Parametric Mapping (SPM) using parametric SUV PET images, and volumes of interest (VOIs) analysis with fronto-parietal, temporal, occipital, and cerebellar SUV background areas were performed to study the effect of age, gender, height, weight, injected activity, body mass index (BMI), and body surface area (BSA). After multivariate analysis, female gender and high BMI were found to be two independent factors associated with increased SUV of F-FET uptake in the brain. In women, SUV of F-FET uptake in the brain was 23% higher than in men (p < 0.01). SUV of F-FET uptake in the brain was positively correlated with BMI (r = 0.29; p < 0.01). The influence of these factors on SUV of F-FET was similar in all brain areas. In conclusion, SUV of F-FET in the normal brain is influenced by gender and weakly by BMI, but changes are similar in all brain areas.
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http://dx.doi.org/10.1016/j.nicl.2017.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684535PMC
June 2018

Cognitive dysfunction associated with aluminum hydroxide-induced macrophagic myofasciitis: A reappraisal of neuropsychological profile.

J Inorg Biochem 2018 04 6;181:132-138. Epub 2017 Oct 6.

INSERM/UPEC U955 Team 10 'Biology of Neuromuscular System', Faculty of Médecine, 94000 Créteil, France; Expert Center for Neuromuscular Diseases, Department of Pathology, Henri Mondor University Hospital, 94000 Créteil, France. Electronic address:

Patients with macrophagic myofasciitis (MMF) present with diffuse arthromyalgias, chronic fatigue, and cognitive disorder. Representative features of MMF-associated cognitive dysfunction include attentional dysfunction, dysexecutive syndrome, visual memory deficit and left ear extinction. Our study aims to reevaluate the neuropsychological profile of MMF. 105 unselected consecutive MMF patients were subjected to a neuropsychological battery of screen short term and long-term memory, executive functions, attentional abilities, instrumental functions and dichotic listening. From these results, patients were classified in four different groups: Subsymptomatic patients (n=41) with performance above pathological threshold (-1.65 SD) in all tests; Fronto-subcortical patients (n=31) who showed pathological results at executive functions and selective attention tests; Papezian patients (n=24) who showed pathological results in storage, recognition and consolidation functions for episodic verbal memory, in addition to fronto-subcortical dysfunction; and Extinction patients (n=9) who had a left ear extinction at dichotic listening test in association to fronto-subcortical and papezian dysfunction. In addition, inter-test analysis showed that patients with apparently normal cognitive functions (Subsymptomatic group) performed significantly worse to attention tests compared to others. In conclusion, our study shows that (i) most patients have specific cognitive deficits; (ii) all patients with cognitive deficit have impairment of executive functions and selective attention; (iii) patients without measurable cognitive deficits display significant weakness in attention; (iv) episodic memory impairment affects verbal, but not visual, memory; (v) none of the patients show an instrumental dysfunction.
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http://dx.doi.org/10.1016/j.jinorgbio.2017.09.019DOI Listing
April 2018

Predictive value of brain 18F-FDG PET/CT in macrophagic myofasciitis?: A case report.

Medicine (Baltimore) 2017 Sep;96(39):e8134

Department of Nuclear Medicine, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University INSERM U955-Team 10 Department of Neurology Department of Pathology, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University Reference Center for Neuromuscular Disorders, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris, Créteil CHU Nancy, Nuclear Medecine and Nancyclotep Experimental Imaging Platform, Nancy INSERM U955-GRC Amyloid Research Institute, Créteil, France.

Rationale: Although several functional studies have demonstrated that positron emission tomography/computed tomography with F-fluorodeoxyglucose (F-FDG PET/CT) appears to be efficient to identify a cerebral substrate in patients with known macrophagic myofasciitis (MMF), the predictive value of this imaging technique for MMF remains unclear.

Patient Concerns: We presented data and images of a 46-year-old woman.

Diagnoses: The patient was referred to our center for suspected MMF due to diffuse arthromyalgias and cognitive disorder (involving an impairment of visual selective attention and a weakness in executive functions revealed by neuropsychological assessment) which occurred few years after last vaccine injections.

Interventions: After a first negative deltoid muscle biopsy, a brain F-FDG PET/CT was performed and revealed the known spatial pattern of a cerebral glucose hypometabolism involving occipital cortex, medial temporal areas, and cerebellum.

Outcomes: Given the clinical suspicion of MMF and brain F-FDG PET/CT findings, a 2nd deltoid muscle biopsy was performed and confirmed the diagnosis of MMF with typical histopathological features.

Lessons: This case highlights the predictive value of brain F-FDG PET/CT as a noninvasive imaging tool for MMF diagnosis, even when muscle biopsy result comes back negative.
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http://dx.doi.org/10.1097/MD.0000000000008134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626290PMC
September 2017

Cerebral 18F-FDG PET in macrophagic myofasciitis: An individual SVM-based approach.

PLoS One 2017 13;12(7):e0181152. Epub 2017 Jul 13.

Department of Nuclear Medicine, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, France.

Introduction: Macrophagic myofasciitis (MMF) is an emerging condition with highly specific myopathological alterations. A peculiar spatial pattern of a cerebral glucose hypometabolism involving occipito-temporal cortex and cerebellum have been reported in patients with MMF; however, the full pattern is not systematically present in routine interpretation of scans, and with varying degrees of severity depending on the cognitive profile of patients. Aim was to generate and evaluate a support vector machine (SVM) procedure to classify patients between healthy or MMF 18F-FDG brain profiles.

Methods: 18F-FDG PET brain images of 119 patients with MMF and 64 healthy subjects were retrospectively analyzed. The whole-population was divided into two groups; a training set (100 MMF, 44 healthy subjects) and a testing set (19 MMF, 20 healthy subjects). Dimensionality reduction was performed using a t-map from statistical parametric mapping (SPM) and a SVM with a linear kernel was trained on the training set. To evaluate the performance of the SVM classifier, values of sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were calculated.

Results: The SPM12 analysis on the training set exhibited the already reported hypometabolism pattern involving occipito-temporal and fronto-parietal cortices, limbic system and cerebellum. The SVM procedure, based on the t-test mask generated from the training set, correctly classified MMF patients of the testing set with following Se, Sp, PPV, NPV and Acc: 89%, 85%, 85%, 89%, and 87%.

Conclusion: We developed an original and individual approach including a SVM to classify patients between healthy or MMF metabolic brain profiles using 18F-FDG-PET. Machine learning algorithms are promising for computer-aided diagnosis but will need further validation in prospective cohorts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181152PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509294PMC
September 2017

Apical sparing pattern of left ventricular myocardial Tc-HMDP uptake in patients with transthyretin cardiac amyloidosis.

J Nucl Cardiol 2018 12 26;25(6):2072-2079. Epub 2017 Apr 26.

Mondor Amyloidosis Network, Créteil, France.

Background: A decreased longitudinal strain in basal segments with a base-to-apex gradient has been described in patients with cardiac amyloidosis (CA).

Objectives: Aim was to investigate the left ventricular (LV) regional distribution of early-phase Tc-Hydroxymethylene diphosphonate (Tc-HMDP) uptake in patients with transthyretin-related cardiac amyloidosis (TTR-CA).

Methods: All patients underwent a whole-body planar Tc-HMDP scintigraphy acquired at 10-min post-injection (early-phase) followed by a thorax SPECT/CT. The segmental uptake (expressed as % of maximal myocardial HMDP uptake) was investigated on the AHA 17-segment model and 3-segment model (basal, mid-cavity, apical).

Results: Sixty-one TTR-CA patients were included of whom 29 were wild-type (wt-TTR-CA) and 32 had hereditary TTR-CA (m-TTR-CA). Early myocardial Tc-HMDP uptake occurred in all TTR-CA. In all patients, segmental analysis of the LV myocardial distribution of Tc-HMDP uptake showed an increased median uptake (interquartile range) in basal/mid-cavity segments compared to the lowest median uptake of apical segments (respectively, 79% [72%-86%] vs. 72% [64%-81%]; P < 10). This pattern was similar in wt-TTR-CA group (78% [70%-84%] vs. 70% [61%-81%]; P < 10), in m-TTR-CA group (80% [74%-86%] vs. 73 [66%-82%]; P < 10) and remained constant independently of the TTR mutation subtype with P ranging 10 to 0.03.

Conclusions: Early-phase myocardial scintigraphy identified regional distribution of Tc-HMDP uptake characterized by a base-to-apex gradient, corroborating echocardiographic, and cardiac magnetic resonance findings. This apical sparing pattern was similar across TTR-CA and TTR mutation subtypes.
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http://dx.doi.org/10.1007/s12350-017-0894-zDOI Listing
December 2018

Brain F-FDG PET Metabolic Abnormalities in Macrophagic Myofasciitis: Are They Stable?

J Nucl Med 2017 09 16;58(9):1532-1533. Epub 2017 Mar 16.

Hôpital Henri Mondor AP-HP 51 Ave. du Mal de Lattre de Tassigny F-94010 Créteil, France E-mail:

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http://dx.doi.org/10.2967/jnumed.117.190876DOI Listing
September 2017

F-FDG PET/CT predicts survival after Y transarterial radioembolization in unresectable hepatocellular carcinoma.

Eur J Nucl Med Mol Imaging 2017 Jul 23;44(7):1215-1222. Epub 2017 Feb 23.

Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.

Purpose: To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 (Y-TARE) for unresectable hepatocellular carcinoma (uHCC).

Methods: We analysed data from 48 patients in our prospective database undergoing Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of F-FDG PET/CT metabolic parameters, including SUV, tumour-to-liver (T/L) uptake ratio and SUV of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses.

Results: The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUV (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUV and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUV and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean SUV; HR 2.6, 95% CI 1.1-5.9, P = 0.02, for median SUV:) and OS (HR 3.2, 95% CI 1-10.9, P = 0.04 for Q1 SUV; HR 3.7, 95% CI 1.1-12.2, P = 0.03, for Q1 T/L uptake ratio), respectively, when testing with either the BCLC staging system or serum AFP level.

Conclusion: Lesion SUV and T/L uptake ratio as assessed by F-FDG PET/CT, but not morphological imaging, were predictive markers of survival in patients undergoing Y-TARE for uHCC.
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http://dx.doi.org/10.1007/s00259-017-3653-0DOI Listing
July 2017

Resin Versus Glass Microspheres for Y Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma Using Pretreatment Partition Model Dosimetry.

J Nucl Med 2017 08 12;58(8):1334-1340. Epub 2017 Jan 12.

Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland.

The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with Y transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD). We performed a retrospective analysis of prospectively collected data on 77 patients consecutively treated (mean age ± SD, 66.4 ± 12.2 y) for uHCC (36 uninodular, 5 multinodular, 36 diffuse) with Y TARE (41 resin, 36 glass) using pretreatment PMD. Study endpoints were progression-free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier estimates. Several variables including Barcelona Clinic Liver Cancer (BCLC) staging system, tumor size, and serum α-fetoprotein (AFP) level were investigated using Cox proportional hazards regression. The characteristics of 2 groups were comparable with regard to demographic data, comorbidities, Child-Pugh score, BCLC, serum AFP level, and Y global administered activity. The median follow-up time was 7.7 mo (range, 0.4-50.1 mo). Relapse occurred in 44 patients (57%) at a median of 6 mo (range, 0.4-27.9 mo) after Y TARE, and 41 patients (53%) died from tumor progression. Comparison between resin and glass microspheres revealed higher but not statistically significantly PFS and OS rates in the Y resin group than the Y glass group (resin PFS 6.1 mo [95% confidence interval CI, 4.7-7.4] and glass PFS 5 mo [95% CI, 0.9-9.2], = 0.53; resin OS 7.7 mo [95% CI, 7.2-8.2] and glass OS 7 mo [95% CI 1.6-12.4], = 0.77). No significant survival difference between both types of Y microspheres was observed in any subgroups of patients with early/intermediate or advanced BCLC stages. Among the variables investigated, Cox analyses showed that only in the glass group, the BCLC staging system and the serum AFP level were associated with PFS ( = 0.04) and OS ( = 0.04). Tumor size was a prognostic factor without significant influence on PFS and OS after Y TARE. Comparison between resin and glass microspheres revealed no significant survival difference in patients treated for uHCC with Y TARE using pretreatment PMD. Further, larger prospective studies are warranted to confirm these findings.
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http://dx.doi.org/10.2967/jnumed.116.184713DOI Listing
August 2017

Early-phase myocardial uptake intensity of Tc-HMDP vs Tc-DPD in patients with hereditary transthyretin-related cardiac amyloidosis.

J Nucl Cardiol 2018 02 1;25(1):217-222. Epub 2016 Nov 1.

Mondor Amyloidosis Network, 94000, Créteil, France.

Background: This study sought to compare the intensity of early-phase myocardial uptake of two phosphonate-based radiotracers, Tc-hydroxymethylene diphosphonate (HMDP) and Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), in patients with hereditary transthyretin-related cardiac amyloidosis (TTR-CA).

Methods: Six patients with biopsy-proven diagnosis of TTR-CA and characteristic amyloid fibril composition underwent early-phase Tc-HMDP myocardial scintigraphy as part of their routine workup; they were later assessed by Tc-DPD scintigraphy after having signed informed written consent. Heart-to-mediastinum-ratio was measured at both time points as well as regional distribution on 17-segment analysis.

Results: All patients had an H/M ratio >1.28 on both imaging. Tc-DPD uptake was slightly higher than Tc-HMDP uptake in 3 patients, but no statistical difference was found (P = 0.13). Regional distribution of the two radiotracers was well correlated on bull's eyes analysis, with only slight underestimation of Tc-DPD uptake in the anterior/apical segments, compared with Tc-HMDP.

Conclusion: Tc-HMDP and Tc-DPD show comparable myocardial uptake intensity on early-phase scintigraphy and can be used alternatively for the diagnosis of TTR-CA.
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http://dx.doi.org/10.1007/s12350-016-0707-9DOI Listing
February 2018

Brain F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

J Nucl Med 2017 03 20;58(3):492-498. Epub 2016 Oct 20.

INSERM U955-Team 10, Créteil, France.

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with F-FDG. F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; = 0.87) and sex (73% women; = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( = 42), those with frontal subcortical (FSC) dysfunction ( = 29), those with Papez circuit dysfunction ( = 22), and those with callosal disconnection ( = 7). In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction.
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http://dx.doi.org/10.2967/jnumed.114.151878DOI Listing
March 2017

68Ga-NODAGA-RGDyK PET/CT Imaging in Esophageal Cancer: First-in-Human Imaging.

Clin Nucl Med 2016 Nov;41(11):e491-e492

From the Departments of *Nuclear Medicine and Molecular Imaging, and †Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland.

Ga-NODAGA-RGDyK(cyclic) and FDG PET/CT were performed in a 39-year-old man for the work-up of a moderately differentiated carcinoma of the gastro-esophageal junction within a clinical study protocol. Although FDG PET images showed intense, diffuse hypermetabolic lesion activity, NODAGA-RGDyK illustrated the neo-angiogenesis process with tracer uptake clearly localized in non-FDG-avid perilesional structures. Neo-angiogenesis is characterized by ανβ3 integrin expression at the lesion surface of newly formed vessels. This case supports evidence that angiogenesis imaging might therefore be a crucial step in early disease identification and localization, metastatization potential, and in monitoring the efficacy of antiangiogenic therapies.
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http://dx.doi.org/10.1097/RLU.0000000000001365DOI Listing
November 2016

F-fluorodeoxyglucose positron emission tomography-computed tomography in the management of adult multisystem Langerhans cell histiocytosis.

Eur J Nucl Med Mol Imaging 2017 Apr 20;44(4):598-610. Epub 2016 Sep 20.

Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

Purpose: The standard evaluation of multisystem Langerhans cell histiocytosis (LCH) includes a clinical evaluation, laboratory tests and a skeleton/skull X-ray survey, with chest high-resolution computed tomography (HRCT) in the case of pulmonary involvement. Preliminary reports suggest that F-fluorodeoxyglucose positron emission tomography-computed tomography (F-FDG PET-CT) may be useful for evaluating patients with LCH.

Methods: Fourteen consecutive adult patients with multisystem LCH were included in this retrospective study, and were evaluated using standard procedures and F-FDG PET-CT. The two sets of findings were compared both at baseline and during follow-up. Serial HRCT and pulmonary function tests were used to evaluate outcome in patients with lung involvement.

Results: At the baseline evaluation, PET-CT identified every LCH localization found with the standard evaluation (except a mild cecum infiltration). PET-CT showed additional lesions in seven patients, mostly involving bones, and differentiated inactive from active lesions. Thyroid F-FDG uptake was identified in three cases. No pituitary stalk F-FDG uptake was observed in patients with pituitary LCH. Only 3/12 (25 %) patients with pulmonary LCH displayed moderate pulmonary F-FDG uptake. During follow-up, variations (≥50 % of maximum standardized uptake) in bone F-FDG uptake intensity were correlated with disease state and response to treatment. The absence of lung F-FDG uptake did not preclude lung function improvement after treatment.

Conclusions: Except for cases with pulmonary and pituitary involvement, F-FDG PET-CT could replace the standard evaluation for staging of adult patients with multisystem LCH. Serial PET-CT scans are useful for evaluating treatment responses, particularly in cases with bone LCH involvement.
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http://dx.doi.org/10.1007/s00259-016-3521-3DOI Listing
April 2017

Brain (18)F-FDG, (18)F-Florbetaben PET/CT, (123)I-FP-CIT SPECT and Cardiac (123)I-MIBG Imaging for Diagnosis of a "Cerebral Type" of Lewy Body Disease.

Nucl Med Mol Imaging 2016 Sep 29;50(3):258-60. Epub 2016 Jan 29.

Department of Nuclear Medicine, AP-HP, Henri-Mondor Teaching Hospital, 51 Ave. du Mal de Lattre de Tassigny, F-94010 Créteil, France.

A 67-year-old man was referred for fluctuating neuropsychiatric symptoms, featuring depression, delirious episodes, recurrent visual hallucinations and catatonic syndrome associated with cognitive decline. No parkinsonism was found clinically even under neuroleptic treatment. (18)F-FDG PET/CT showed hypometabolism in the posterior associative cortex including the occipital cortex, suggesting Lewy body dementia, but (123)I-FP-CIT SPECT was normal and cardiac (123)I-MIBG imaging showed no signs of sympathetic denervation. Alzheimer's disease was excluded by a normal (18)F-florbetaben PET/CT. This report suggests a rare case of α-synucleinopathy without brainstem involvement, referred to as "cerebral type" of Lewy body disease.
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http://dx.doi.org/10.1007/s13139-016-0394-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977251PMC
September 2016

[Cardiac sarcoidosis: seven keypoints to remind in order to avoid misdiagnosis].

Rev Med Suisse 2016 May;12(520):1035-6, 1038-41

Early diagnosis of cardiac sarcoidosis remains difficult in the absence of specific symptoms. The evolution and prognosis of the disease are strongly correlated to an early and appropriate treatment. The multi-modality assessment based on cardiac MRI and positron emission tomography associated with computed tomography (PET/CT) has significantly improved the detection of cardiac sarcoidosis over the last two decades. These approaches appear as useful and suitable imaging strategy for the early diagnosis, the assessment of the disease extent as well as the management and therapeutic follow-up. This article is a didactic review on cardiac sarcoidosis, with a special focus on recent diagnostic and therapeutic modalities, prognosis and interest of imaging techniques.
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May 2016

Grey-Matter Metabolism in Relation with White-Matter Lesions in Older Hypertensive Patients with Subjective Memory Complaints: A Pilot Voxel-Based Analysis Study.

Cerebrovasc Dis 2016 13;42(1-2):106-9. Epub 2016 Apr 13.

Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU-Nancy, Nancy, France.

Background: This study aimed at assessing the changes in brain metabolism related to white-matter magnetic resonance (MR) hyperintensities of presumed vascular origin, with a voxel-based quantitative analysis of (18F)-fluorodesoxyglucose positron emission tomography (FDG-PET) imaging.

Methods: Sixty older hypertensive patients with subjective memory complaints (75 ± 5 years, 34 women) were prospectively referred to FDG-PET and MRI brain imaging. The Statistical Parametric Mapping software was used to assess the correlation between brain distribution of FDG and white-matter hyperintensities assessed by the Fazekas score on MRI images.

Results: The Fazekas score was inversely related to FDG uptake, independently of age and gender, within 14 Brodmann areas located mainly in the frontal lobe but also in certain limbic, insular and temporal areas. This relationship was also found to be largely independent of the volume of grey matter expressed in percentage of cranial volume, an index of atrophy.

Conclusions: White-matter MR hyperintensities of presumed vascular origin are cross-sectionally associated with a lower grey-matter metabolism, mainly but not only within frontal areas and independently of age, gender and grey-matter atrophy.
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http://dx.doi.org/10.1159/000445527DOI Listing
November 2017

Metabolic Tumour Burden Measured by 18F-FDG PET/CT Predicts Malignant Transformation in Patients with Neurofibromatosis Type-1.

PLoS One 2016 17;11(3):e0151809. Epub 2016 Mar 17.

Department of Nuclear Medicine, H. Mondor Hospital, Assistance Publique-Hôpitaux de Paris/Paris-Est University, Créteil, F-94010.

Background: To investigate the diagnostic and prognostic performances of 18F-FDG PET/CT measures of metabolic tumour burden in patients with neurofibromatosis type-1 (NF1), suspect of malignant transformation.

Methods: This retrospective study included 49 patients (15-60 years old, 30 women) with a diagnosis of NF1, followed in our Reference Centre for Rare Neuromuscular Diseases, who presented clinical signs of tumour progression (pain, neurological deficit, tumour growth). Quantitative metabolic parameters were measured on 149 tumoral targets, using semi-automatic software and the best cut off values to predict transformation was assessed by Receiver Operating Characteristics (ROC) analysis. Prognostic value of PET/CT metabolic parameters was assessed by Kaplan-Meier estimates of overall survival.

Results: Lesions were histologically documented in 40 patients: a sarcomatous transformation was found in 16, a dysplastic neurofibroma (NF) in 7, and a benign NF in 17; in the remaining 9 patients, a minimal follow-up of 12 mo (median 59 mo) confirmed the absence of transformation. The optimal cut off values for detection of malignant transformation were, in decreasing order of area under the ROC curves, a tumour-to-liver (T/L) ratio >2.5, SUVmax > 4.5, total lesion glycolysis (TLG) > 377, total metabolic tumour volume (TMTV) > 88 cm3, and heterogeneity index (HIsuv) > 1.69. The best prognostic marker was the TLG: the 4-y estimates of survival were 97% [95% CI, 90% - 100%] in patients with TLG ≤ 377 vs. 27% [95% CI, 5% - 49%] in patients with TLG > 377 (P < 0.0001; χ2 27.85; hazard ratio 13.27 [95% CI, 3.72-47.35]). T/L ratio, SUVmax and TMTV demonstrated slightly lower performance to predict survival, with χ2 ranging 14.41-19.12. The HIsuv index was not predictive of survival.

Conclusion: Our study demonstrates that TLG and TMTV, as PET/CT measures of metabolic tumour burden, may be used clinically to identify sarcomatous transformation in patients with NF1 and predict overall survival, with a higher specificity for the TLG. Conventional measures such as the SUVmax, and T/L ratio also demonstrate high prognostic value.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151809PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795780PMC
July 2016

FDG-PET/CT Brain Findings in a Patient With Macrophagic Myofasciitis.

Nucl Med Mol Imaging 2016 Mar 23;50(1):80-4. Epub 2015 Sep 23.

Department of Nuclear Medicine, Hôpital Henri Mondor AP-HP, Paris-Est University, 51 Ave. du Mal de Lattre de Tassigny, F-94010 Créteil, France.

Brain Positron Emission Tomography/Computed Tomography with (18)F-fluorodeoxyglucose (FDG PET/CT) was performed in a 44-year-old woman with marked cognitive impairment, diffuse myalgias, sensory, memory and visual disorders, and chronic fatigue, presenting with histopathological features of macrophagic myofasciitis (MMF) at deltoid muscle biopsy. Cerebromedullary Magnetic Resonance Imaging (MRI), electromyography, ophthalmic examination, and cerebrospinal fluid analysis were normal. Visual analysis of FDG PET/CT images showed an atypical pattern of hypometabolism, involving symmetrically the occipital cortex, temporal lobes, and limbic system (including in particular amygdalo-hippocampal complexes), and the cerebellum. Posterior cingulate cortex and parietal areas were preserved. This pattern was confirmed by a voxel-based procedure using Statistical Parametric Mapping (SPM12) that compared a patient's images to normal reference samples from six healthy subjects with adjustment to age obtained using the same PET/CT camera. These results provide a glucose metabolism substrate for cognitive complaints in patients with long-lasting aluminium hydroxide-induced MMF.
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http://dx.doi.org/10.1007/s13139-015-0371-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762870PMC
March 2016

Temporal epilepsy lesions may be detected by the voxel-based quantitative analysis of brain FDG-PET images using an original block-matching normalization software.

Ann Nucl Med 2016 May 3;30(4):272-8. Epub 2016 Feb 3.

Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHU-Nancy, 54000, Nancy, France.

Introduction: Statistical parametric mapping (SPM) provides useful voxel-by-voxel analyses of brain images from (18)F-fluorodesoxyglucose positron emission tomography (FDG-PET) after an initial step of spatial normalization through an anatomical template model. In the setting of the preoperative workup of patients with temporal epilepsy, this study aimed at assessing a block-matching (BM) normalization method, where most transformations are computed through small blocks, a principle that minimizes artefacts and overcomes additional image-filtering.

Methods: Brain FDG-PET images from 31 patients with well-characterised temporal lobe epilepsy and among whom 22 had common mesial temporal lobe epilepsy were retrospectively analysed using both BM and conventional SPM normalization methods and with PET images from age-adjusted controls. Different threshold p values corrected for cluster volume were considered (0.01, 0.005, and 0.001).

Results: The use of BM provided equivalent values to those of SPM with regard to the overall volumes of temporal and extra-temporal hypometabolism, as well as similar sensitivity for detecting the involved temporal lobe, reaching 87 and 94 % for SPM and BM, respectively, at a threshold p value of 0.01. However, the ability to more accurately localize brain lesions within the mesial portion of the temporal lobe was a little higher with BM than with SPM with respective sensitivities reaching 78 % for BM and 45 % for SPM (p < 0.05).

Conclusions: BM normalization compares well with conventional SPM for the voxel-based quantitative analysis of the FDG-PET images from temporal epilepsy patients. Further studies in different population are needed to determine whether BM is truly an accurate alternative to SPM in this setting.
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http://dx.doi.org/10.1007/s12149-016-1060-4DOI Listing
May 2016

Usefulness of (99m)Tc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis.

Amyloid 2015 14;22(4):210-20. Epub 2015 Oct 14.

a UPEC , Créteil , France .

Background: Amyloidosis is characterized by extracellular deposits of insoluble proteins that cause tissue damage. The three main types are monoclonal light chain (AL), wild-type transthyretin (wt-TTR) and mutated transthyretin (m-TTR) amyloidosis. Cardiac amyloidosis (CA) raises diagnostic challenges.

Objective: To assess the diagnostic accuracy of (99m)Tc-HMDP-scintigraphy for typing CA, differentiating CA from non-amyloid left ventricle hypertrophy (LVH), and predicting outcomes.

Methods: 121 patients with suspected CA underwent (99m)Tc-HMDP-scintigraphy in addition to standard investigations.

Results: CA was diagnosed in all AL (n = 14) and wt-TTR (n = 21). Among m-TTR (n = 34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls. (99m)Tc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two and in one AL. A visual score ≥ 2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic and scintigraphic variables, NYHA III-IV and HR/SR > 1.94 predicted acute heart failure and/or death.

Conclusions: This preliminary study suggests that (99m)Tc-HMDP-scintigraphy may aid differentiation between transthyretin and AL-CA as well as CA from other LVHs. (99m)Tc-HMDP-scintigraphy appears to provide prognostic information in CA.
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http://dx.doi.org/10.3109/13506129.2015.1072089DOI Listing
October 2016

[18F]-NaF PET/CT imaging in cardiac amyloidosis.

J Nucl Cardiol 2016 08 24;23(4):846-9. Epub 2015 Sep 24.

UPEC, AP-HP Henri-Mondor Teaching Hospital, 94000, Créteil, France.

Cardiac amyloidosis (CA) is recognized as a common cause of restrictive cardiomyopathy and heart failure due to the deposition of insoluble proteins in the myocardial interstitium. We emphasize the role of [18F]-sodium fluoride (NaF) PET/CT as a potential noninvasive tool to identify and differentiate the transthyretin-related cardiac amyloidosis from the light-chain cardiac amyloidosis. We report cases of a 73-year-old man and a 75-year-old woman followed in our center for congestive heart failure with marked alteration of the left ventricular ejection fraction due to familial transthyretin Val122Ile cardiac amyloidosis and light-chain cardiac amyloidosis, respectively, confirmed on endomyocardial biopsy.
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http://dx.doi.org/10.1007/s12350-015-0287-0DOI Listing
August 2016