Comparison of the prognostic value of impaired stress myocardial blood flow, myocardial flow reserve, and myocardial flow capacity on low-dose Rubidium-82 SiPM PET/CT.

BACKGROUND: The most reliable quantitative variable on Rubidium-82 (82Rb) cardiac PET/CT for predicting major adverse cardiovascular events (MACE) has not been characterized with low-dose silicon photomultipliers (SiPM) technology, which allows halving injected activity and radiation dose delivering less than 1.0 mSv in a 70-kg individual. METHODS AND RESULTS: We prospectively enrolled 234 consecutive participants with suspected myocardial ischemia. Participants underwent 82Rb cardiac SiPM PET/CT (5 MBq/kg) and were followed up for MACE over 652 days (interquartile range 559-751 days). For each participant, global stress myocardial blood flow (stress MBF), global myocardial flow reserve (MFR), and regional severely reduced myocardial flow capacity (MFCsevere) were measured. The Youden index was used to select optimal thresholds. In multivariate analysis after adjustments for clinical risk factors, reduced global stress MBF < 1.94 ml/min/g, reduced global MFR < 1.98, and regional MFCsevere > 3.2% of left ventricle emerged all as independent predictors of MACE (HR 4.5, 3.1, and 3.67, respectively, p < 0.001). However, only reduced global stress MBF remained an independent prognostic factor for MACE after adjusting for clinical risk factors and the combined use of global stress MBF, global MFR, and regional MFCsevere impairments (HR 2.81, p = 0.027). CONCLUSION: Using the latest SiPM PET technology with low-dose 82Rb halving the standard activity to deliver < 1 mSv for a 70-kg patient, impaired global stress MBF, global MFR, and regional MFC were powerful predictors of cardiovascular events, outperforming traditional cardiovascular risk factors. However, only reduced global stress MBF independently predicted MACE, being superior to global MFR and regional MFC impairments.

[Good Psychiatric Management for Borderline Personality Disorder - A Specialized Treatment Applicable in General Care]. / «Good Psychiatric Management¼ pour le trouble de la personnalité borderline - Un traitement spécialisé applicable aux soins généralistes.

This article presents basic notions of "Good Psychiatric Management" (GPM) for Borderline Personality Disorder (BPD). There have been several evidence-based psychotherapeutic treatments for BPD for several decades. Nevertheless, high requirements and motivation required sometimes have a discouraging effect for trainees. GPM aims at offering «good enough¼ and less difficult to implement care. This article presents the notion of Interpersonnal Hypersensitivity and its different attachment states (attached, threatened, abandoned, and desperate) describing internal coherence of BPD and founding therapeutic interventions. GPM is principle based, thus is highly adaptable, as can be seen in integration with other intervention models or implementation of stepped care.

Cet article présente les bases du «Good Psychiatric Management¼ (GPM) pour le trouble de la personnalité borderline. Il existe pour ce trouble différents traitements psychothérapeutiques fondés sur les preuves. Les exigences importantes que ceux-ci représentent en termes de formation et de motivation ont parfois comme effet de décourager les thérapeutes en formation. Le GPM décrit des soins «suffisamment bons¼, accessibles et moins difficiles à implanter. Cet article présente le concept d'hypersensibilité interpersonnelle qui décrit la cohérence interne du trouble et fonde les interventions thérapeutiques. Le GPM est basé sur l'application de principes, ce qui lui donne une adaptabilité importante, par exemple pour l'intégration avec d'autres modèles d'intervention ou des soins par paliers.

Implanted System for Orthostatic Hypotension in Multiple-System Atrophy.

Orthostatic hypotension is a cardinal feature of multiple-system atrophy. The upright posture provokes syncopal episodes that prevent patients from standing and walking for more than brief periods. We implanted a system to restore regulation of blood pressure and enable a patient with multiple-system atrophy to stand and walk after having lost these abilities because of orthostatic hypotension. This system involved epidural electrical stimulation delivered over the thoracic spinal cord with accelerometers that detected changes in body position. (Funded by the Defitech Foundation.).

A knock-in rat model unravels acute and chronic renal toxicity in glutaric aciduria type I.

Glutaric aciduria type I (GA-I, OMIM # 231670) is an autosomal recessive inborn error of metabolism caused by deficiency of the mitochondrial enzyme glutaryl-CoA dehydrogenase (GCDH). The principal clinical manifestation in GA-I patients is striatal injury most often triggered by catabolic stress. Early diagnosis by newborn screening programs improved survival and reduced striatal damage in GA-I patients. However, the clinical phenotype is still evolving in the aging patient population. Evaluation of long-term outcome in GA-I patients recently identified glomerular filtration rate (GFR) decline with increasing age. We recently created the first knock-in rat model for GA-I harboring the mutation p.R411W (c.1231 C>T), corresponding to the most frequent GCDH human mutation p.R402W. In this study, we evaluated the effect of an acute metabolic stress in form of high lysine diet (HLD) on young Gcdhki/ki rats. We further studied the chronic effect of GCDH deficiency on kidney function in a longitudinal study on a cohort of Gcdhki/ki rats by repetitive 68Ga-EDTA positron emission tomography (PET) renography, biochemical and histological analyses. In young Gcdhki/ki rats exposed to HLD, we observed a GFR decline and biochemical signs of a tubulopathy. Histological analyses revealed lipophilic vacuoles, thinning of apical brush border membranes and increased numbers of mitochondria in proximal tubular (PT) cells. HLD also altered OXPHOS activities and proteome in kidneys of Gcdhki/ki rats. In the longitudinal cohort, we showed a progressive GFR decline in Gcdhki/ki rats starting at young adult age and a decline of renal clearance. Histopathological analyses in aged Gcdhki/ki rats revealed tubular dilatation, protein accumulation in PT cells and mononuclear infiltrations. These observations confirm that GA-I leads to acute and chronic renal damage. This raises questions on indication for follow-up on kidney function in GA-I patients and possible therapeutic interventions to avoid renal damage.

Impact of prophylactic cranial irradiation and hippocampal sparing on 18F-FDG brain metabolism in small cell lung cancer patients.

BACKGROUND AND PURPOSE: Prophylactic cranial irradiation (PCI) in small-cell lung cancer (SCLC) patients improves survival. However, it is also associated with cognitive impairment, although the underlying mechanisms remain poorly understood. Our study aims to evaluate the impact of PCI and potential benefit of hippocampal sparing (HS) on brain metabolism assessed by 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT). MATERIALS AND METHODS: We retrospectively included 22 SCLC patients. 50% had hippocampal-sparing (HS) PCI. 18F-FDG PET/CT was performed 144.5 ± 73 days before and 383 ± 451 days after PCI. Brain 18F-FDG PET scans were automatically segmented in 12 regions using Combined-AAL Atlas from MI-Neurology Software (Syngo.Via, Siemens Healthineers). For all atlas regions, we computed SUV Ratio using brainstem as a reference region (SUVR = SUVmean/Brainstem SUVmean) and compared SUVR before and after PCI, using a Wilcoxon test, with a level of significance of p < 0.05. RESULTS: We found significant decreases in 18F-FDG brain metabolism after PCI in the basal ganglia (p = 0.004), central regions (p = 0.001), cingulate cortex (p < 0.001), corpus striata (p = 0.003), frontal cortex (p < 0.001), parietal cortex (p = 0.001), the occipital cortex (p = 0.002), precuneus (p = 0.001), lateral temporal cortex (p = 0.001) and cerebellum (p < 0.001). Conversely, there were no significant changes in the mesial temporal cortex (MTC) which includes the hippocampi (p = 0.089). The subgroup who received standard PCI showed a significant decrease in metabolism of the hippocampi (p = 0.033). Contrastingly, the subgroup of patients who underwent HS-PCI showed no significant variation in metabolism of the hippocampi (p = 0.783). CONCLUSION: PCI induced a diffuse decrease in 18F-FDG brain metabolism. HS-PCI preserves metabolic activity of the hippocampi.

The use of 68Ga-EDTA PET allows detecting progressive decline of renal function in rats.

INTRODUCTION: Evaluation of glomerular filtration rate is very important in both preclinical and clinical setting, especially in the context of chronic kidney disease. It is typically performed using 51Cr-EDTA or by imaging with 123I-Hippuran scintigraphy, which has a significantly lower resolution and sensitivity as compared to PET. 68Ga-EDTA represents a valid alternative due to its quick availability using a 68Ge/68Ga generator, while PET/CT enables both imaging of renal function and accurate quantitation of clearance of activity from both plasma and urine. Therefore, we aimed at investigating the use of 68Ga-EDTA as a preclinical tracer for determining renal function in a knock-in rat model known to present progressive decline of renal function. METHODS: 68Ga-EDTA was injected in 23 rats, either wild type (n=10) or knock-in (n=13). By applying a unidirectional, two-compartment model and Rutland-Patlak Plot linear regression analysis, split renal function was determined from the age of 6 weeks to 12 months. RESULTS: Glomerular filtration ranged from 0.025±0.01 ml/min at 6 weeks to 0.049±0.05 ml/min at 6 months in wild type rats. Glomerular filtration was significantly lower in knock-in rats at 6 and 12 months (P<0.01). No significant difference was observed in renal volumes between knock-in and wild type animals, based on imaging-derived volume calculations. CONCLUSIONS: 68Ga-EDTA turned out to be a very promising PET/CT tracer for the evaluation of split renal function. This method allowed detection of progressive renal impairment in a knock-in rat model. Additional validation in a human cohort is warranted to further assess clinical utility in both, healthy individuals and patients with renal impairment.

Appropriate use criteria for dementia amyloid imaging in Switzerland - mini-review and statement on behalf of the Swiss Society of Nuclear Medicine and the Swiss Memory Clinics.

While FDG-PET imaging of the brain for the differential diagnosis of dementia has been covered by the compulsory health insurance in Switzerland for more than a decade, beta-amyloid-PET just recently has been added to the catalogue of procedures that have been cleared for routine use, provided that a set of appropriate use criteria (AUC) be followed. To provide guidance to dementia care practitioners, the Swiss Society of Nuclear Medicine and the Swiss Memory Clinics jointly report a mini-review on beta-amyloid-PET and discuss the AUC set into effect by the Swiss Federal Office of Public Health, as well as their application and limitations.

Diagnostic Performance of 18F-FDG PET/CT in Native Valve Endocarditis: Systematic Review and Bivariate Meta-Analysis.

BACKGROUND: Infectious endocarditis is a life-threatening disease, requiring prompt and accurate diagnosis. The aim of this article is to perform a systematic review and meta-analysis of the literature to estimate the performance of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for the diagnosis of native valve endocarditis (NVE). METHODS: Selected articles evaluating the diagnostic accuracy of 18F-FDG PET/CT in patients with suspected NVE, resulting from a comprehensive literature search through the PubMed/MEDLINE and Cochrane library databases until April 2020, were included for the systematic review and meta-analysis. RESULTS: Seven studies (351 episodes of suspected NVE) were included. 18F-FDG PET/CT yielded a pooled sensitivity of 36.3% and a pooled specificity of 99.1% for the diagnosis of NVE. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 8.3, 0.6, and 15.3, respectively. The sensitivity increased using contemporary PET/CT device with state-of-the-art patient preparation as well as innovative image acquisitions or adding the results of 18F-FDG PET/CT in a multimodality strategy. CONCLUSIONS: In our systematic review and meta-analysis, 18F-FDG PET/CT yielded a poor pooled sensitivity with an otherwise excellent pooled specificity for the diagnosis of NVE; however, several factors may increase the sensitivity without affecting the specificity and these factors should be better evaluated in future studies.

Increased 18F-FDG signal recovery from small physiological structures in digital PET/CT and application to the pituitary gland.

On conventional PET/CT, and under physiological conditions, the volume of the pituitary gland (PG) is small, and its metabolic activity is commonly comparable to the surrounding background level in 18F-FDG imaging. We compared the physiological 18F-FDG uptake of the PG in patients imaged with digital PET (dPET) and with conventional PET (cPET). Additionally, we performed phantom experiments to characterize signal recovery and detectability of small structures. We retrospectively included 10 dPET and 10 cPET patients and measured PG SUVmax, SUVmean and SUVratio (using cerebellum as reference). We imaged a modified NEMA/IEC phantom with both dPET and cPET (background activity 5 kBq/mL, and 3× and 5× higher concentrations in ∅2-20-mm spherical inserts). Mean recovery coefficients (RCmean) and signal-difference-to-noise-ratio (SDNR) were computed to assess lesion detectability. Patients imaged with dPET presented higher PG SUVmax and SUVratio (SUVR) compared to patients imaged with cPET (4.7 ± 2.05 vs. 2.9 ± 0.64, p = 0.004; and 0.62 ± 0.25 vs 0.39 ± 0.09, p = 0.029, respectively), while there was no difference for SUVmean (2.7 ± 1.32 vs 2.1 ± 0.44, p = 0.39). Thus, with a SUV readout scale of 0-5 g/mL, normal PG appeared abnormally hot with dPET, but not with cPET. Phantom evidenced higher RCmean in dPET compared to cPET. For both 3x and 5x measurements, lesion detectability according to size was systematically superior with dPET. In conclusion, patients imaged with dPET presented higher 18F-FDG physiological uptake of the PG as compared to patients imaged with cPET. These findings were supported by phantom experiments demonstrating superior signal recovery and small region detectability with dPET. Awareness of this new "higher" SUV of the normal 18F-FDG uptake of the PG is important to avoid potential pitfalls in image interpretation, notably in oncologic patients treated with immunotherapy, who are at increased risk to develop hypophysitis.

Dialectical behavior therapy skills training affects defense mechanisms in borderline personality disorder: An integrative approach of mechanisms in psychotherapy.

Objective: Borderline personality disorder (BPD) is characterized by immature defense mechanisms. Dialectical behavior therapy (DBT) is an effective treatment for BPD. However, understanding the underlying mechanisms of change is still limited. Using a transtheoretical framework, we investigated the effect of DBT skills training on defense mechanisms. Method: In this randomized controlled trial, 16 of 31 BPD outpatients received DBT skills training adjunctive to individual treatment as usual (TAU), while the remaining 15 received only individual TAU. Pre-post changes of defense mechanisms, assessed with the Defense Mechanism Rating Scale, were compared between treatment conditions using ANCOVAs. Partial correlations and linear regressions were conducted to explore associations between defenses and symptom outcome. Results: Overall defense function improved significantly more in the skills training condition (F(1, 28) = 4.57, p = .041). Borderline defenses decreased throughout skills training, but not throughout TAU only (F(1, 28) = 5.09, p = .032). In the skills training condition, an increase in narcissistic defenses was associated with higher symptom scores at discharge (ß = 0.58, p = .02). Conclusions: Although DBT does not explicitly target defense mechanisms, skills training may have favorable effects on defense function in BPD. Our findings contribute to an integrative understanding of mechanisms of change in BPD psychotherapy.

Change in Emotional and Theory of Mind Processing in Borderline Personality Disorder: A Pilot Study.

Changes in emotional processing (EP) and in theory of mind (TOM) are central across treatment approaches for patients with borderline personality disorder (BPD). Although the assessment of EP relies on the observation of a patient's self-criticism in a two-chair dialogue, an individual's TOM assessments is made based on responses to humorous stimuli based on false beliefs. For this pilot study, we assessed eight patients with BPD before and after a 3-month-long psychiatric treatment, using functional magnetic resonance imaging and behavioral tasks. We observed arousal increase within the session of the two-chair dialogue (d = 0.36), paralleled by arousal decrease between sessions (d = 0.80). We found treatment-associated trends for neural activity reduction in brain areas central for EP and TOM. Our exploratory findings using an integrative assessment procedure of changes in EP and TOM point toward evidence for treatment effects at the brain systems level related to behavioral modulation.

[Cardiac sarcoidosis: seven keypoints to remind in order to avoid misdiagnosis]. / Sarcoïdose cardiaque: sept points à rappeler pour ne pas manquer le diagnostic.

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.

FDG-PET hyperactivity pattern in anti-NMDAr encephalitis.

FDG-PET can show anteroposterior glucose metabolism gradient in anti-NMDAr encephalitis, but there are also suggestions that basal ganglia are involved. We examined FDG-PET scans in 5 consecutive episodes of serologically proven anti-NMDAr encephalitis, compared with healthy controls. We confirmed the anteroposterior metabolic gradient and found a significant FDG uptake increase in the caudate nuclei in episodes of varying intensity and delay from the onset of the symptoms. FDG-PET can be useful in the work-up of suspected anti-NMDAr encephalitis disclosing a characteristic cortical and sub-cortical metabolism pattern.

Thoracic fat volume is independently associated with coronary vasomotion.

PURPOSE: Thoracic fat has been associated with an increased risk of coronary artery disease (CAD). As endothelium-dependent vasoreactivity is a surrogate of cardiovascular events and is impaired early in atherosclerosis, we aimed at assessing the possible relationship between thoracic fat volume (TFV) and endothelium-dependent coronary vasomotion. METHODS: Fifty healthy volunteers without known CAD or major cardiovascular risk factors (CRFs) prospectively underwent a (82)Rb cardiac PET/CT to quantify myocardial blood flow (MBF) at rest, and MBF response to cold pressor testing (CPT-MBF) and adenosine (i.e., stress-MBF). TFV was measured by a 2D volumetric CT method and common laboratory blood tests (glucose and insulin levels, HOMA-IR, cholesterol, triglyceride, hsCRP) were performed. Relationships between CPT-MBF, TFV and other CRFs were assessed using non-parametric Spearman rank correlation testing and multivariate linear regression analysis. RESULTS: All of the 50 participants (58 ± 10y) had normal stress-MBF (2.7 ± 0.6 mL/min/g; 95 % CI: 2.6-2.9) and myocardial flow reserve (2.8 ± 0.8; 95 % CI: 2.6-3.0) excluding underlying CAD. Univariate analysis revealed a significant inverse relation between absolute CPT-MBF and sex (ρ = -0.47, p = 0.0006), triglyceride (ρ = -0.32, p = 0.024) and insulin levels (ρ = -0.43, p = 0.0024), HOMA-IR (ρ = -0.39, p = 0.007), BMI (ρ = -0.51, p = 0.0002) and TFV (ρ = -0.52, p = 0.0001). MBF response to adenosine was also correlated with TFV (ρ = -0.32, p = 0.026). On multivariate analysis, TFV emerged as the only significant predictor of MBF response to CPT (p = 0.014). CONCLUSIONS: TFV is significantly correlated with endothelium-dependent and -independent coronary vasomotion. High TF burden might negatively influence MBF response to CPT and to adenosine stress, even in persons without CAD, suggesting a link between thoracic fat and future cardiovascular events.

Effects of continuous positive airway pressure treatment on coronary vasoreactivity measured by (82)Rb cardiac PET/CT in obstructive sleep apnea patients.

PURPOSE: Obstructive sleep apnea syndrome (OSA) increases the risk of cardiovascular disease. We aimed at evaluating the effect of continuous positive airway pressure (CPAP) treatment on coronary endothelium-dependent vasoreactivity in OSA patients by quantifying myocardial blood flow (MBF) response to cold pressure testing (CPT). METHODS: In the morning after polysomnography (PSG), all participants underwent a dynamic (82)Rb cardiac positron emitting tomography/computed tomography (PET/CT) scan at rest, during CPT and adenosine stress. PSG and PET/CT were repeated at least 6 weeks after initiating CPAP treatment. OSA patients were compared to controls and according to response to CPAP. Patients' characteristics and PSG parameters were used to determine predictors of CPT-MBF. RESULTS: Thirty-two untreated OSA patients (age 58 ± 13 years, 27 men) and 9 controls (age 62 ± 5 years, 4 men) were enrolled. At baseline, compared to controls (apnea-hypopnea index (AHI) = 5.3 ± 2.6/h), untreated OSA patients (AHI = 48.6 ± 19.7/h) tend to have a lower CPT-MBF (1.1 ± 0.2 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.09). After initiating CPAP, CPT-MBF was not different between well-treated patients (AHI <10/h) and controls (1.3 ± 0.3 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.83), but it was lower for insufficiently treated patients (AHI ≥10/h) (0.9 ± 0.2 mL/min/g vs. 1.3 ± 0.4 mL/min/g, p = 0.0045). CPT-MBF was also higher in well-treated than in insufficiently treated patients (1.3 ± 0.3 mL/min/g vs. 0.9 ± 0.2 mL/min/g, p = 0.001). Mean nocturnal oxygen saturation (ß = -0.55, p = 0.02) and BMI (ß = -0.58, p = 0.02) were independent predictors of CPT-MBF in OSA patients. CONCLUSIONS: Coronary endothelial vasoreactivity is impaired in insufficiently treated OSA patients compared to well-treated patients and controls, confirming the need for CPAP optimization.

Myocardial blood flow quantification by Rb-82 cardiac PET/CT: A detailed reproducibility study between two semi-automatic analysis programs.

BACKGROUND: Several analysis software packages for myocardial blood flow (MBF) quantification from cardiac PET studies exist, but they have not been compared using concordance analysis, which can characterize precision and bias separately. Reproducible measurements are needed for quantification to fully develop its clinical potential. METHODS: Fifty-one patients underwent dynamic Rb-82 PET at rest and during adenosine stress. Data were processed with PMOD and FlowQuant (Lortie model). MBF and myocardial flow reserve (MFR) polar maps were quantified and analyzed using a 17-segment model. Comparisons used Pearson's correlation ρ (measuring precision), Bland and Altman limit-of-agreement and Lin's concordance correlation ρc = ρ·C b (C b measuring systematic bias). RESULTS: Lin's concordance and Pearson's correlation values were very similar, suggesting no systematic bias between software packages with an excellent precision ρ for MBF (ρ = 0.97, ρc = 0.96, C b = 0.99) and good precision for MFR (ρ = 0.83, ρc = 0.76, C b = 0.92). On a per-segment basis, no mean bias was observed on Bland-Altman plots, although PMOD provided slightly higher values than FlowQuant at higher MBF and MFR values (P < .0001). CONCLUSIONS: Concordance between software packages was excellent for MBF and MFR, despite higher values by PMOD at higher MBF values. Both software packages can be used interchangeably for quantification in daily practice of Rb-82 cardiac PET.

Added prognostic value of myocardial blood flow quantitation in rubidium-82 positron emission tomography imaging.

AIMS: We studied the respective added value of the quantitative myocardial blood flow (MBF) and the myocardial flow reserve (MFR) as assessed with (82)Rb positron emission tomography (PET)/CT in predicting major adverse cardiovascular events (MACEs) in patients with suspected myocardial ischaemia. METHODS AND RESULTS: Myocardial perfusion images were analysed semi-quantitatively (SDS, summed difference score) and quantitatively (MBF, MFR) in 351 patients. Follow-up was completed in 335 patients and annualized MACE (cardiac death, myocardial infarction, revascularization, or hospitalization for congestive heart failure or de novo stable angor) rates were analysed with the Kaplan-Meier method in 318 patients after excluding 17 patients with early revascularizations (<60 days). Independent predictors of MACEs were identified by multivariate analysis. During a median follow-up of 624 days (inter-quartile range 540-697), 35 MACEs occurred. An annualized MACE rate was higher in patients with ischaemia (SDS >2) (n = 105) than those without [14% (95% CI = 9.1-22%) vs. 4.5% (2.7-7.4%), P < 0.0001]. The lowest MFR tertile group (MFR <1.8) had the highest MACE rate [16% (11-25%) vs. 2.9% (1.2-7.0%) and 4.3% (2.1-9.0%), P < 0.0001]. Similarly, the lowest stress MBF tertile group (MBF <1.8 mL/min/g) had the highest MACE rate [14% (9.2-22%) vs. 7.3% (4.2-13%) and 1.8% (0.6-5.5%), P = 0.0005]. Quantitation with stress MBF or MFR had a significant independent prognostic power in addition to semi-quantitative findings. The largest added value was conferred by combining stress MBF to SDS. This holds true even for patients without ischaemia. CONCLUSION: Perfusion findings in (82)Rb PET/CT are strong MACE outcome predictors. MBF quantification has an added value allowing further risk stratification in patients with normal and abnormal perfusion images.

Longer intervals between hematopoietic stem cell transplantation and subsequent 90Y-ibritumomab radioimmunotherapy may correlate with better tolerance.

PURPOSE: This study aimed to evaluate the efficacy and toxicity of radioimmunotherapy (RIT) in recurrent lymphoma after hematopoietic stem cell transplantation (HSCT). METHODS: We reviewed 9 patients, 7 with follicular lymphoma (DLBCL), 1 with mantle cell lymphoma (MCL), and 1 with diffuse large B-cell lymphoma treated with 90Y-ibritumomab tiuxetan 6 to 140 months after HSCT. Patients underwent 111In-ibritumomab scintigraphy and were treated 1 week later with standard 14.8 MBq/kg (n = 4) or 11.1 MBq/kg (n = 4) 90Y-ibritumomab. One patient who had allo-HSCT had reduced activity (70%) treatment. RESULTS: Among the 7 FL patients, we observed complete response (CR) in 2 patients and partial response (PR) in 5 patients. One patient with CR relapsed after 15 months; the other persisted 43.5 months after RIT. Of 5 patients with PR, 3 relapsed between 13 and 17 months; 1 persisted until unrelated death at 11.5 months. The fifth patient with PR received adoptive immunotherapy and improved to metabolic (FDG-PET) CR that persists 45.5 and 41 months after 90Y-ibritumomab and immunotherapy, respectively. Patients with MCL and DLBCL progressed or experienced stabilization (5 months), respectively. Six patients had grade 1 to 3 bone marrow (BM) toxicity and recovered within 3 months. Three patients having 90Y-ibritumomab 6, 14, and 24 months after HSCT experienced grade 4 BM toxicity. One of them (RIT 24 months after HSCT) recovered after 3 months, another delayed after 9 months, and the third patient only partially recovered, eventually developed myelodysplasia, and was allografted. CONCLUSIONS: Radioimmunotherapy after HSCT is an effective rescue therapy in FL. However, BM toxicity may be important; 3 of 8 patients treated with standard 90Y-ibritumomab activity experienced grade 4 BM toxicity, with incomplete recovery 3 months after RIT in 2 patients, both treated early (6 and 14 months) after HSCT.

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water.

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.

Assessment of coronary vasoreactivity by multidetector computed tomography: feasibility study with rubidium-82 cardiac positron emission tomography.

BACKGROUND: Positron emission tomography (PET) during the cold pressor test (CPT) has been used to assess endothelium-dependent coronary vasoreactivity, a surrogate marker of cardiovascular events. However, its use remains limited by cardiac PET availability. As multidetector computed tomography (MDCT) is more widely available, we aimed to develop a measurement of endothelium-dependent coronary vasoreactivity with MDCT and similar radiation burden as with PET. METHODS AND RESULTS: A study group of 18 participants without known cardiovascular risk factor (9F/9M; age 60±6 years) underwent cardiac PET with (82)Rb and unenhanced ECG-gated MDCT within 4h, each time at rest and during CPT. The relation between absolute myocardial blood flow (MBF) response to CPT by PET (ml·min(-1)·g(1)) and relative changes in MDCT-measured coronary artery surface were assessed using linear regression analysis and Spearman's correlation. MDCT and PET/CT were analyzed in all participants. Hemodynamic conditions during CPT at MDCT and PET were similar (P>0.3). Relative changes in coronary artery surface because of CPT (2.0-21.2%) correlated to changes in MBF (-0.10-0.52ml·min(-1)·g(1)) (ρ=0.68, P=0.02). Effective dose was 1.3±0.2mSv for MDCT and 3.1mSv for PET/CT. CONCLUSIONS: Assessment of endothelium-dependent coronary vasoreactivity using MDCT CPT appears feasible. Because of its wider availability, shorter examination time and similar radiation burden, MDCT could be attractive in clinical research for coronary status assessment.