Measuring myocardial blood flow using dynamic myocardial perfusion SPECT: artifacts and pitfalls.

Dynamic acquisition allows absolute quantification of myocardial perfusion and flow reserve, offering an alternative to overcome the potential limits of relative quantification, especially in patients with balanced multivessel coronary artery disease. SPECT myocardial perfusion is widely available, at lower cost than PET. Dynamic cardiac SPECT is now feasible and has the potential to be the next step of comprehensive perfusion imaging. In order to help nuclear cardiologists potentially interested in using dynamic perfusion SPECT, we sought to review the different steps of acquisition, processing, and reporting of dynamic SPECT studies in order to enlighten the potentially critical pitfalls and artifacts. Both patient-related and technical artifacts are discussed. Key parameters of the acquisition include pharmacological stress, radiopharmaceuticals, and injection device. When it comes to image processing, attention must be paid to image-derived input function, patient motion, and extra-cardiac activity. This review also mentions compartment models, cameras, and attenuation correction. Finally, published data enlighten some facets of dynamic cardiac SPECT while several issues remain. Harmonizing acquisition and quality control procedures will likely improve its performance and clinical strength.

Definition of left ventricular remodelling following ST-elevation myocardial infarction: a systematic review of cardiac magnetic resonance studies in the past decade.

An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI), but without consensual definition. We aimed to review the criteria used for the definition of LVR based on cardiac magnetic resonance imaging (CMR) in STEMI patients. A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving 4209 patients were included. Among these studies, 30 (81%) used a cut-off value for defining LVR, with a pooled LVR prevalence estimate of 22.8%, 95% CI [19.4-26.7%] and a major between-study heterogeneity (I2 = 82%). The seven remaining studies (19%) defined LVR as a continuous variable. The definition of LVR using CMR following STEMI is highly variable, among studies including highly selected patients. A 20% increase or a 15% increase in left ventricular volumes between a baseline and a follow-up CMR imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). The most frequent LVR criterion was a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12 to 15% increase in end-systolic volume and a 12 to 20% increase in end-diastolic volume using a follow-up CMR imaging 3 months after STEMI might be proposed as a consensual cut-off for defining adverse LVR for future large-sized, prospective studies with serial CMR imaging and long-term follow-up in unselected patients.

Quantitation of myocardial 99mTc-HMDP uptake with new SPECT/CT cadmium zinc telluride (CZT) camera in patients with transthyretin-related cardiac amyloidosis: Ready for clinical use?

BACKGROUND: The aim of this study was to investigate the feasibility of assessing absolute myocardial 99mTc-HMDP uptake in patients with suspected cardiac ATTR using SUV with a whole-body CZT SPECT-CT camera (DNM670CZT). METHODS: Fifteen patients with suspected cardiac ATTR (Perugini ≥ 2) underwent a conventional 99mTc-HMDP planar imaging and a thoracic SPECT/CT using a DNM 670CZT. A control group consisted of 15 patients with negative scintigraphy (Perugini < 2). SUVmax (mg·L-1) and percentage of injected dose (%ID) were calculated in a cardiac volume of interest (VOI) encompassing the left ventricle. VOIs were also placed in the lung, the right pectoris major, and the sternum. A heart-to-lung SUVmax ratio (HLR) was calculated. RESULTS: All ATTR patients demonstrated an increased cardiac HMDP SUVmax (12.2 ± 3.7 mg·L-1) vs controls (3.5 ± 1.2, P < .0001). Percentage of ID, pectoral uptake and HLR were significantly higher in the ATTR group (1.1 ± 0.3 vs 0.15 ± 0.8, P < .0001; 1.5 ± 0.3 vs 0.9 ± 0.3, P < .0001; 9.7 ± 3 vs 4.3 ± 2.2, P < .0001). Bone uptake was not statistically different between the two groups. CONCLUSION: This study demonstrated the feasibility of quantitative 99mTc-HMDP SUVmax measurement using a whole-body SPECT/CT CZT camera in patients with suspected cardiac ATTR.

Left atrial strain quantified after myocardial infarction is associated with early left ventricular remodeling.

BACKGROUND: Left ventricular remodeling (LVR) is common and associated with adverse outcome after ST-elevation myocardial infarction (STEMI). We aimed to investigate the association between left atrial (LA) mechanical function using speckle tracking imaging and early LVR at follow-up in STEMI patients. METHODS: Baseline 3D thoracic echocardiograms were performed within 48 h following admission and at a median follow-up of 7 months after STEMI. A > 20% increase in the left ventricular (LV) end-diastolic volume compared to baseline at follow-up was defined as LVR. LA global longitudinal strain was evaluated for the reservoir, conduit, and contraction (LASct) phases. RESULTS: A total of 121 patients without clinical heart failure (HF) were prospectively included, between June 2015 and October 2018 (age 58.3 ± 12.5 years, male 98 (81%)). Baseline and follow-up LV ejection fraction (LVEF) were 46.8% [41.0, 52.9] and 52.1% [45.8, 57.0] respectively (p < .001). Compared to other patients, those with LVR had significantly lower values of LASct at baseline (-7.4% [-10.1, -6.5] vs. -9.9% [-12.8, -8.1], p < .01), both on univariate and baseline LV volumes-adjusted analyses. Baseline LA strain for reservoir and conduit phases were not associated with significant LVR at follow-up. Intra- and interobserver analysis showed good reproducibility of LA strain. CONCLUSIONS: Baseline LASct may help identifying patients without HF after STEMI who are at higher risk of further early LVR and subsequent HF and who may benefit from more intensive management.

Steroid-sparing effect of anakinra in giant-cell arteritis: a case series with clinical, biological and iconographic long-term assessments.

OBJECTIVES: The treatment of GCA relies on corticosteroids but is burdened by a high rate of relapses and adverse effects. Anti-IL-6 treatments show a clear benefit with a significant steroid-sparing effect, but late relapses occur after treatment discontinuation. In addition to IL-6, IL-1 also appears to play a significant role in GCA pathophysiology. We report herein the efficacy of anakinra, an IL-1 receptor antagonist, in six GCA patients exhibiting corticosteroid dependence or resistance, specifically analysing the outcome of aortitis in four of them. METHODS: This retrospective study analysed the cases of all GCA patients treated with anakinra from the French Study Group for Large Vessel Vasculitis. RESULTS: After a median duration of anakinra therapy of 19 (18-32) months, all six patients exhibited complete clinical and biological remission. Among the four patients with large-vessel involvement, one had a disappearance of aortitis under anakinra and three showed a decrease in vascular uptake. After a median follow-up of 56 (48-63) months, corticosteroids were discontinued in four patients, and corticosteroid dosage could be decreased to 5 mg/day in two patients. One patient relapsed 13 months after anakinra introduction in the context of increasing the daily anakinra injection interval to every 48 h. Three patients experienced transient injection-site reactions, and one patient had pneumonia. CONCLUSION: In this short series, anakinra appears to be an efficient and safe steroid-sparing agent in refractory GCA, with a possible beneficial effect on large-vessel involvement.

Quantification of myocardial blood flow by CZT-SPECT with motion correction and comparison with 15O-water PET.

BACKGROUND: We compared quantification of MBF and myocardial flow reserve (MFR) with a 99mTc-sestamibi CZT-SPECT to 15O-water PET. METHODS: SPECT MBF for thirty patients in the WATERDAY study was re-analyzed by QPET software with motion correction and optimal placement of the arterial input function. 15O-water PET MBF was re-quantified using dedicated software. Inter-operator variability was assessed using repeatability coefficients (RPC). RESULTS: Significant correlations were observed between global (r = 0.91, P < 0.001) and regional MBF (r = 0.86, P < 0.001) with SPECT compared to PET. Global MBF (rest 0.95 vs 1.05 ml/min/g, P = 0.07; stress 2.62 vs 2.68 mL/min/g, P = 0.17) and MFR (2.65 vs 2.75, P = 0.86) were similar between SPECT and PET. Rest (0.81 vs 0.98 mL/min/g, P = 0.03) and stress MBF (1.98 vs 2.61 mL/min/g, P = 0.01) in right coronary artery (RCA) were lower with SPECT compared to PET. However, MFR in the RCA territory was similar (2.54 vs 2.77, P = 0.21). The SPECT-PET RPC for global MBFs and MFR were 0.95 mL/min/g and 0.94, with inter-observer RPC of 0.59 mL/min/g and 0.74, respectively. CONCLUSIONS: MBF and MFR derived from CZT-SPECT with motion correction and optimal placement of the arterial input function showed good agreement with 15O-water PET, as well as low inter-operator variability.

Impaired left atrial function in adults and adolescents with corrected aortic coarctation.

This study examined the left atrial (LA) function using two-dimensional (2D) strain analysis after aortic coarctation (CoA) repair, as well as relationships between LA function and patient characteristics, especially aortic arch anatomy. 56 patients (34 males, age: 31 ± 16 years) with CoA repair (46 post 'end-to-end anastomosis/subclavian flap') and 56 controls were studied. 2D strain imaging was performed to assess left ventricular (LV) and LA functions including peak-positive LA strain, early and late diastolic LA strains, and global longitudinal (LV-GLS) and circumferential (LV-GCS) strains. LA dysfunction (LAD) was defined as a peak-positive LA strain value lower than the mean value of the control group minus 2 SDs. Peak-positive LA strain, early and late diastolic LA strains, and LV-GLS were significantly lower in the CoA group while LV-GCS did not differ. No significant correlation was found between LA strain and either current age, age at initial repair, or blood pressure; Ea and LV-GLS were moderately correlated to peak-positive LA strain (r = 0.49, p < 0.001 and r = - 0.55, p < 0.001, respectively). 23 CoA patients (41%) presented LAD (abnormal peak-positive LA strain < 25%). Among patients who underwent end-to-end anastomosis/subclavian flap, those with a non-romanesque aortic arch anatomy exhibited a significantly lower peak-positive LA strain. Ischemic stroke and atrial arrhythmia were more frequent in CoA patients with LAD. Our findings suggest that LAD may be prevalent late after CoA repair. Postoperative aortic arch anatomy may impact peak-positive LA strain.

TRPM4 non-selective cation channel in human atrial fibroblast growth.

Cardiac fibroblasts play an important role in cardiac matrix turnover and are involved in cardiac fibrosis development. Ca2+ is a driving belt in this phenomenon. This study evaluates the functional expression and contribution of the Ca2+-activated channel TRPM4 in atrial fibroblast phenotype. Molecular and electrophysiological investigations were conducted in human atrial fibroblasts in primary culture and in atrial fibroblasts obtained from wild-type and transgenic mice with disrupted Trpm4 gene (Trpm4-/-). A typical TRPM4 current was recorded on human cells (equal selectivity for Na+ and K+, activation by internal Ca2+, voltage sensitivity, conductance of 23.2 pS, inhibition by 9-phenanthrol (IC50 = 6.1 × 10-6 mol L-1)). Its detection rate was 13% on patches at days 2-4 in culture but raised to 100% on patches at day 28. By the same time, a cell growth was observed. This growth was smaller when cells were maintained in the presence of 9-phenanthrol. Similar cell growth was measured on wild-type mice atrial fibroblasts during culture. However, this growth was minimized on Trpm4-/- mice fibroblasts compared to control animals. In addition, the expression of alpha smooth muscle actin increased during culture of atrial fibroblasts from wild-type mice. This was not observed in Trpm4-/- mice fibroblasts. It is concluded that TRPM4 participates in fibroblast growth and could thus be involved in cardiac fibrosis.

First comparison of performances between the new whole-body cadmium-zinc-telluride SPECT-CT camera and a dedicated cardiac CZT camera for myocardial perfusion imaging: Analysis of phantom and patients.

BACKGROUND: Dedicated cardiac Cadmium-zinc-telluride (CZT) cameras show superior performances compared with Anger systems, particularly in terms of spatial resolution and count sensitivity. This study evaluated the performances of a new polyvalent whole body CZT camera (DNM 670CZT) compared with a cardiac dedicated CZT camera (DNM 530c) for myocardial perfusion SPECT. METHODS: The spatial resolution was evaluated with three linear sources filled with 99mTc. We used a cardiac phantom to evaluate count sensitivity, sharpness index, contrast-to-noise ratio, wall thickness, non-uniformity index, perfusion scores and ventricle volumes for both cameras. The impact of matrix size, and acquisition time was investigated. Concordance between the two cameras was evaluated in patients using QPS/QGS software for quantitative segmental perfusion, motion and thickness scores. RESULTS: The spatial resolution was identical with the two cameras. Count sensitivity of the DNM 670CZT was twofold lower compared with the DNM 530c, leading to lower sharpness index and contrast-to-noise ratio. The wall thickness and the myocardial volumes were similar. Visual and quantitative assessments of the perfusion patterns have shown a good concordance of the two cameras on phantoms and in patients. CONCLUSION: This study demonstrated the feasibility of myocardial perfusion SPECT imaging using the new whole-body DNM 670CZT camera.

Comparison of the dyssynchrony parameters recorded with gated SPECT in ischemic cardiomyopathy according to their repeatability at rest and to their ability to detect a synchrony reserve under dobutamine infusion.

BACKGROUND: This study aimed to determine whether the repeatability of dyssynchrony assessment using gated myocardial perfusion SPECT (GSPECT) allows the detection of synchrony reserve during low-dose dobutamine infusion. METHODS AND RESULTS: Sixty-one patients with ischemic cardiomyopathy and LV ejection fraction < 50% were prospectively included in 10 centers. Each patient underwent two consecutive rest GSPECT with 99mTc-labeled tracer (either tetrofosmin or sestamibi) to assess the repeatability of LV function and dyssynchrony parameters, followed by a GSECT acquisition during low-dose dobutamine infusion. LV dyssynchrony was assessed using QGS software through histogram bandwidth (BW), standard deviation of the phase (SD), and entropy. Repeatability was assessed with Lin's concordance correlation coefficient (CCC). Entropy showed a higher CCC (0.80) compared to BW (0.68) and SD (0.75). On average, dobutamine infusion yielded to improve both BW (P = .049) and entropy (P = .04) although significant improvements, setting outside the 95% confidence interval of the repeatability analysis, were documented in only 6 and 4 patients for BW and entropy, respectively. CONCLUSIONS: A synchrony reserve may be documented in patients with ischemic cardiomyopathy through the recording of BW and entropy with low-dose dobutamine GSPECT, with the additional advantage of a higher repeatability for entropy.

Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction.

BACKGROUND: Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). METHODS: We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. RESULTS: Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126-450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). CONCLUSIONS: Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.

Different patterns and specific outcomes of large-vessel involvements in giant cell arteritis.

Large-vessel involvement (LVI) in giant cell arteritis (GCA) includes different clinical and imaging patterns that are rarely described separately at diagnosis and whose specific cardiovascular outcomes are unknown. We conducted a nationwide retrospective study and included GCA patients with LVI demonstrated on imaging at diagnosis between 2007 and 2017. We analyzed the prognosis of three different imaging patterns of LVI present at diagnosis, with some of them overlapping but with the first one present in all patients: 1) inflammation of the aorta and/or its branches; 2) dilation of the aorta; and 3) stenosis of the aortic branches. A control group of GCA patients without LVI was constituted. We included 183 patients with LVI and 105 controls without LVI. Altogether, among the 183 patients who all showed inflammation of the aorta and/or its main branches, concomitant aortic dilation and large-vessel stenosis were observed in 27 (15%) and 55 (30%) patients, respectively. During the follow-up period, new cardiovascular events occurred in 49% and 11% of LVI patients and controls, respectively (p < 0.0001). Inflammation of the aorta and/or its branches (HR: 3.42 [2.09-5.83], p < 0.0001) and large-artery stenosis (HR: 2.75 [1.80-4.15], p < 0.0001) were independent predictive factors of new cardiovascular events. Conversely, the use of an immunosuppressant besides corticosteroids was a protective factor against new cardiovascular events (HR: 0.44 [0.29-0.66], p < 0.0001) and the development of aortic dilation (HR: 0.43 [0.23-0.77], p = 0.005). This study suggests different forms of cardiovascular events according to the initial imaging pattern of LVI.

First validation of myocardial flow reserve assessed by dynamic 99mTc-sestamibi CZT-SPECT camera: head to head comparison with 15O-water PET and fractional flow reserve in patients with suspected coronary artery disease. The WATERDAY study.

PURPOSE: We assessed the feasibility of myocardial blood flow (MBF) and flow reserve (MFR) estimation using dynamic SPECT with a novel CZT camera in patients with stable CAD, in comparison with 15O-water PET and fractional flow reserve (FFR). METHODS: Thirty patients were prospectively included and underwent FFR measurements in the main coronary arteries (LAD, LCx, RCA). A stenosis ≥50% was considered obstructive and a FFR abnormal if ≤0.8. All patients underwent a dynamic rest/stress 99mTc-sestamibi CZT-SPECT and 15O-water PET for MBF and MFR calculation. Net retention kinetic modeling was applied to SPECT data to estimate global uptake values, and MBF was derived using Leppo correction. Ischemia by PET and CZT-SPECT was considered present if MFR was lower than 2 and 2.1, respectively. RESULTS: CZT-SPECT yielded higher stress and rest MBF compared to PET for global and LAD and LCx territories, but not in RCA territory. MFR was similar in global and each vessel territory for both modalities. The sensitivity, specificity, accuracy, positive and negative predictive value of CZT-SPECT were, respectively, 83.3, 95.8, 93.3, 100 and 85.7% for the detection of ischemia and 58.3, 84.6, 81.1, 36.8 and 93% for the detection of hemodynamically significant stenosis (FFR ≤ 0.8). CONCLUSIONS: Dynamic 99mTc-sestamibi CZT-SPECT was technically feasible and provided similar MFR compared to 15O-water PET and high diagnostic value for detecting impaired MFR and abnormal FFR in patients with stable CAD.

First assessment of simultaneous dual isotope (123I/99mTc) cardiac SPECT on two different CZT cameras: A phantom study.

BACKGROUND: We studied the impact of simultaneous dual-isotope acquisition on 123I/99mTc mismatch assessment using two CZT cameras (DNM 530c, GE Healthcare and DSPECT, Biosensors International). METHODS: We used an anthropomorphic torso phantom (respectively filled with a solution of 123I alone, 99mTc alone, and a mixture of 123I and 99mTc) and its cardiac insert with two defects mimicking two matched and mismatched defects. Mismatch extent and reconstructed image contrast were evaluated. RESULTS: The acquisition mode (single vs dual) significantly impacted (i) 99mTc (but not 123I) reconstructed segmental activities using both camera (P < .001), and (ii) image contrast (using 123I and DNM 530c, P < .0001; and using both 123I and 99mTc with DSPECT, P < .0001). However, the defect and mismatch size were not impacted by the type of acquisition. With both DNM 530c and DSPECT, Lin's concordance correlation coefficient and Bland-Altman analysis demonstrated an almost perfect concordance and agreement between single- and simultaneous dual-isotope segmental activity (123I and 99mTc). CONCLUSIONS: This study found no impact of the acquisition mode (single vs dual) or the type of camera (DSPECT vs DNM 530c) on 123I and 99mTc defect size and mismatch, providing a new step toward simultaneous dual-isotope acquisition for combined innervation and perfusion assessment.

Giant-cell arteritis: concordance study between aortic CT angiography and FDG-PET/CT in detection of large-vessel involvement.

PURPOSE: The purpose of our study was to assess the concordance of aortic CT angiography (CTA) and FDG-PET/CT in the detection of large-vessel involvement at diagnosis in patients with giant-cell arteritis (GCA). METHODS: We created a multicenter cohort of patients with GCA diagnosed between 2010 and 2015, and who underwent both FDG-PET/CT and aortic CTA before or in the first ten days following treatment introduction. Eight vascular segments were studied on each procedure. We calculated concordance between both imaging techniques in a per-patient and a per-segment analysis, using Cohen's kappa concordance index. RESULTS: We included 28 patients (21/7 women/men, median age 67 [56-82]). Nineteen patients had large-vessel involvement on PET/CT and 18 of these patients also presented positive findings on CTA. In a per-segment analysis, a median of 5 [1-7] and 3 [1-6] vascular territories were involved on positive PET/CT and CTA, respectively (p = 0.03). In qualitative analysis, i.e., positivity of the procedure suggesting a large-vessel involvement, the concordance rate between both procedures was 0.85 [0.64-1]. In quantitative analysis, i.e., per-segment analysis in both procedures, the global concordance rate was 0.64 [0.54-0.75]. Using FDG-PET/CT as a reference, CTA showed excellent sensitivity (95%) and specificity (100%) in a per-patient analysis. In a per-segment analysis, sensitivity and specificity were 61% and 97.9%, respectively. CONCLUSIONS: CTA and FDG-PET/CT were both able to detect large-vessel involvement in GCA with comparable results in a per-patient analysis. However, PET/CT showed higher performance in a per-segment analysis, especially in the detection of inflammation of the aorta's branches.

[18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis.

PURPOSE: Hypoxia in gliomas is associated with tumor resistance to radio- and chemotherapy. However, positron emission tomography (PET) imaging of hypoxia remains challenging, and the validation of biological markers is, therefore, of great importance. We investigated the relationship between uptake of the PET hypoxia tracer [18F]-FMISO and other markers of hypoxia and angiogenesis and with patient survival. PATIENTS AND METHODS: In this prospective single center clinical study, 33 glioma patients (grade IV: n = 24, III: n = 3, and II: n = 6) underwent [18F]-FMISO PET and MRI including relative cerebral blood volume (rCBV) maps before surgery. Maximum standardized uptake values (SUVmax) and hypoxic volume were calculated, defining two groups of patients based on the presence or absence of [18F]-FMISO uptake. After surgery, molecular quantification of CAIX, VEGF, Ang2 (rt-qPCR), and HIF-1α (immunohistochemistry) were performed on tumor specimens. RESULTS: [18F]-FMISO PET uptake was closely linked to tumor grade, with high uptake in glioblastomas (GB, grade IV). Expression of biomarkers of hypoxia (CAIX, HIF-1α), and angiogenesis markers (VEGF, Ang2, rCBV) were significantly higher in the [18F]-FMISO uptake group. We found correlations between the degree of hypoxia (hypoxic volume and SUVmax) and expression of HIF-1α, CAIX, VEGF, Ang2, and rCBV (p < 0.01). Patients without [18F]-FMISO uptake had a longer survival time than uptake positive patients (log-rank, p < 0.005). CONCLUSIONS: Tumor hypoxia as evaluated by [18F]-FMISO PET is associated with the expression of hypoxia markers on a molecular level and is related to angiogenesis. [18F]-FMISO uptake is a mark of an aggressive tumor, almost always a glioblastoma. Our results underline that [18F]-FMISO PET could be useful to guide glioma treatment, and in particular radiotherapy, since hypoxia is a well-known factor of resistance.

Sustained quality of life improvement after intracoronary injection of autologous bone marrow cells in the setting of acute myocardial infarction: results from the BONAMI trial.

PURPOSE: Cardiac cell therapy is a promising treatment for acute myocardial infarction (AMI), leading to cardiac function improvement. However, whether it translates into quality of life (QoL) improvement is unclear. We hypothesized that administration of bone marrow cells (BMC) to patients with AMI improves QoL. METHODS: In the multicenter BONAMI trial (NCT00200707), patients with reperfused AMI and decreased myocardial viability were randomized to intracoronary autologous BMC infusion (n = 52) or state-of-the-art therapy (n = 49). QoL data, derived from the Minnesota Living with Heart Failure questionnaire (MLHFQ), were obtained 1, 3, and 12 months after AMI and analyzed using a Rasch-family model. RESULTS: Using this model, QoL improved over time in the BMC group (p = 0.025) but not in the control group. Furthermore, the BMC-group patients displayed a better QoL than the control-group patients at 3 and 12 months post-AMI (p = 0.034 and p = 0.003, respectively). These findings were not detected when analyzing MLHFQ data using a standard method. Cardiac function, myocardial viability, mortality, and number of major adverse cardiac events did not differ between treatment groups. CONCLUSION: Our results suggest that BMC therapy can improve QoL, stressing the need for confirmation trials and for systematic QoL assessment in cardiac cell therapy trials .

TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

KEY POINTS: The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. ABSTRACT: Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias.

Assessment of endothelial function and myocardial flow reserve using (15)O-water PET without attenuation correction.

PURPOSE: Myocardial blood flow (MBF) measurement using positron emission tomography (PET) from the washout rate of (15)O-water is theoretically independent of tissue attenuation. The aim of this study was to evaluate the impact of not using attenuation correction in the assessment of coronary endothelial function and myocardial flow reserve (MFR) using (15)O-water PET. METHODS: We retrospectively processed 70 consecutive (15)O-water PET examinations obtained at rest and during cold pressor testing (CPT) in patients with dilated cardiomyopathy (n = 58), or at rest and during adenosine infusion in heart transplant recipients (n = 12). Data were reconstructed with attenuation correction (AC) and without attenuation correction (NAC) using filtered backprojection, and MBF was quantified using a single compartmental model. The agreement between AC and NAC data was assessed using Lin's concordance correlation coefficient followed by Bland-Altman plot analysis. RESULTS: Regarding endothelial function, NAC PET showed poor reproducibility and poor agreement with AC PET data. Conversely, NAC PET demonstrated high reproducibility and a strong agreement with AC PET for the assessment of MFR. CONCLUSION: Non-attenuation-corrected (15)O-water PET provided an accurate measurement of MFR compared to attenuation-corrected PET. However, non-attenuation-corrected PET data were less effective for the assessment of endothelial function using CPT in this population.