Relative Perfusion Research Articles

Rest/stress myocardial perfusion imaging by positron emission tomography with 18F-Flurpiridaz: A feasibility study in mice

BackgroundMyocardial perfusion imaging by positron emission tomography (PET-MPI) is the current gold standard for quantification of myocardial blood flow. 18F-flurpiridaz was recently introduced as a valid alternative to currently used PET-MPI probes. Nonetheless, optimum scan duration and time interval for image analysis are currently unknown. Further, it is unclear whether rest/stress PET-MPI with 18F-flurpiridaz is feasible in mice. MethodsRest/stress PET-MPI was performed with 18F-flurpiridaz (0.6-3.0 MBq) in 27 mice aged 7–8 months. Regadenoson (0.1 µg/g) was used for induction of vasodilator stress. Kinetic modeling was performed using a metabolite-corrected arterial input function. Image-derived myocardial 18F-flurpiridaz uptake was assessed for different time intervals by placing a volume of interest in the left ventricular myocardium. ResultsTracer kinetics were best described by a two-tissue compartment model. K1 ranged from 6.7 to 20.0 mL·cm−3·min−1, while myocardial volumes of distribution (VT) were between 34.6 and 83.6 mL·cm−3. Of note, myocardial 18F-flurpiridaz uptake (%ID/g) was significantly correlated with K1 at rest and following pharmacological vasodilation for all time intervals assessed. However, while Spearman’s coefficients (rs) ranged between 0.478 and 0.681, R2 values were generally low. In contrast, an excellent correlation of myocardial 18F-flurpiridaz uptake with VT was obtained, particularly when employing the averaged myocardial uptake from 20 to 40 min post tracer injection (R2 ≥ 0.98). Notably, K1 and VT were similarly sensitive to pharmacological vasodilation induction. Further, mean stress-to-rest ratios of K1, VT, and %ID/g 18F-flurpiridaz were virtually identical, suggesting that %ID/g 18F-flurpiridaz can be used to estimate coronary flow reserve (CFR) in mice. ConclusionOur findings suggest that a simplified assessment of relative myocardial perfusion and CFR, based on image-derived tracer uptake, is feasible with 18F-flurpiridaz in mice, enabling high-throughput mechanistic CFR studies in rodents.

Use of ICG Angiography in Head and Neck Reconstruction With the Supraclavicular Artery Island Flap

Adequate distal skin paddle perfusion is essential to preventing postoperative flap necrosis in head and neck reconstruction. To describe the use of indocyanine green angiography (ICGA), to assess skin paddle perfusion in the setting of head and neck reconstruction with the supraclavicular artery island flap at a single institution and assess the effect of ICGA use on the rate of postoperative skin paddle necrosis. A retrospective cohort study consistently of patients who underwent head and neck reconstruction with a supraclavicular artery island flap for any indication at a tertiary medical center from 2010 to 2018. The predictor variable was ICGA use. The primary outcome was rate of skin paddle necrosis. Secondary outcomes included rates of post-operative overall complications, dehiscence, fistula, and reoperation. Covariates included demographic, operative, flap perfusion assessment, and postoperative variables. Retrospective assessment of distal flap perfusion was performed on available ICGA video recordings. Descriptive and bivariate statistics were computed. Statistical significance was set at P≤.05. A total of 104 patients were included and ICGA was used in 23 cases. In 10 of these cases, flap trimming was performed due to concern of flap hypoperfusion on ICGA. The median relative distal flap perfusion was 16.7±2.6% in trimmed flaps, compared to 35±13.2% in untrimmed flaps. ICGA use was not associated with rate of skin paddle necrosis (P=.76). ICGA is a viable method of assessing intraoperative supraclavicular artery island skin paddle perfusion and can help determine the need for distal flap trimming when tissue viability based on clinical findings alone is uncertain. ICGA use for skin paddles with uncertain perfusion on intraoperative clinical findings prevented a potential increase in postoperative necrosis compared to that of skin paddles with adequate perfusion on intraoperative clinical findings. Future studies are required to determine the minimum distal perfusion value that indicates hypoperfusion and the need for flap modification.

In This Issue of the Journal

In This Issue of the Journal

Development, diagnostic performance, and interobserver agreement of a 18F-flurpiridaz PET automated perfusion quantitation system

BackgroundComputerized methodologies standardize the myocardial perfusion imaging (MPI) interpretation process. MethodsTo develop an automated relative perfusion quantitation approach for 18F-flurpiridaz, PET MPI studies from all phase III trial participants of 18F-flurpiridaz were divided into 3 groups. Count distributions were obtained in N = 40 normal patients undergoing pharmacological or exercise stress. Then, N = 90 additional studies were selected in a derivation group. Following receiver operating characteristic curve analysis, various standard deviations below the mean normal were used as cutoffs for significant CAD, and interobserver variability determined. Finally, diagnostic performance was compared between blinded visual readers and blinded derivations of automated relative quantitation in the remaining N = 548 validation patients. ResultsBoth approaches yielded comparable accuracies for the detection of global CAD, reaching 71% and 72% by visual reads, and 72% and 68% by automated relative quantitation, when using CAD ≥ 70% or ≥ 50% stenosis for significance, respectively. Similar results were observed when analyzing individual coronary territories. In both pharmacological and exercise stress, automated relative quantitation demonstrated significantly more interobserver agreement than visual reads. ConclusionsOur automated method of 18F-flurpiridaz relative perfusion analysis provides a quantitative, objective, and highly reproducible assessment of PET MPI in normal and CAD subjects undergoing either pharmacological or exercise stress.

Activity regimes for 82Rb cardiac PET: Effects on absolute MBF and MPI

BackgroundSelection of optimal tracer activity for 82Rb PET is based on a trade-off between necessary count-statistics in the late static phase and detector saturation in the early blood-pool phase. Administered tracer activity recommended in prescribing information differs substantially from recommendations in current literature. The present study examines the effect on both absolute myocardial blood flow (MBF), myocardial flow reserve (MFR) and relative myocardial perfusion imaging (MPI) of reducing dose. MethodsForty patients were scanned twice on a PMT-based PET/CT (GE D690): At recommended activity (1110 MBq) and at either 740 or 370 MBq. MBF, MFR, total perfusion deficit (TPD) and ejection fractions (EF) were quantified. Results were compared using linear regression and Bland–Altman plots. ResultsLinear correlation between MBF at 1110 MBq at either reduced activity had an R2 > 0.98. A small bias (± 5%-9%) was observed with opposite signs for 1110/740 and 1110/370. Limits of agreement for MBF were larger for 1110/370. MFR had a lower linear correlation (R2 = 0.96), but wide limits of agreement especially for 1110/370. TPD and EF correlated well at 1110/740 (R2 = 0.96 and 0.99, respectively), but large scatter was observed for 1110/370. ConclusionReduction of the tracer activity to 740 MBq, significantly reduced dead-time correction factors, while still producing reliable static and gated images. However, despite large dead-time at 1110 MBq, no systematic bias on absolute MBF was observed compared to reduced activities.

Common Ictal and Interictal Perfusion Patterns: A Window into the Epileptogenic Network and SUDEP Mechanism in Drug-Resistant Focal Epilepsy.

Focal epilepsies have been described as a network disease. Noninvasive investigative techniques have been used to characterize epileptogenic networks. This study aimed to describe ictal and interictal cortical and subcortical perfusion patterns using single- photon emission computed tomography (SPECT) in patients with drug-resistant epilepsy (DRE). Thirty-five interictal-ictal SPECT scans were obtained from 15 patients with DRE. A methodology was developed to get a relative perfusion index (PI) of 74 cortical and sub-cortical brain structures. K-means algorithm, together with modified v-fold cross-validation, was used to identify the two regions of interest (ROIs) that represent hypoperfused and hyperperfused areas. In common with the individual analysis, the statistical analysis evidenced that the hyperperfusion ROIs resulting from group analysis during interictal and ictal involved mainly the cingulate gyrus, cuneus, lingual gyrus, and gyrus rectus as well as the putamen. ROIs hypoperfused included the red nucleus, the substantia nigra, and the medulla. The medians of the group analysis of the hypoperfusion and hyperperfusion ROIs were 0.601-0.565 and 1.133-1.119 for the ictal and interictal states, correspondingly. A group of mostly cortical structures involved in the hyperperfused ROIs in both interictal and ictal states showed no change or negative change in the transition from interictal to ictal state (mean change of -0.002). On the other hand, the brain stem, basal ganglia, red nucleus, and thalamus revealed a mean global change of 0.19, indicating a mild increase in the PI. However, some of these structures (red nucleus, substantia nigra, and medulla oblongata) remained hypoperfused during the interictal to ictal transition. The methodology employed made it possible to identify common cortical and subcortical perfusion patterns not directly linked to epileptogenicity, for a better epileptogenic network and sudden unexpected death (SUDEP) mechanism in DRE.

The Mystery of Inappropriate Hypoxia After Single Lung Transplant

<h3>Introduction</h3> Single lung transplantation (SLT) is a treatment option for end stage lung disease in select patients, increasing utilization of a scarce resource. Increase in relative perfusion to the allograft from hypoxic vasoconstriction typically ameliorates hypoxia despite native lung disease. We present a SLT recipient with idiopathic pulmonary fibrosis (IPF) who developed hypoxia due to inappropriate shunting to the native lung after an IPF exacerbation. <h3>Case Report</h3> A 66 year old female with IPF had a left SLT eight months prior to presentation. Four months post transplant, she developed submassive bilateral extensive pulmonary embolism (PE) requiring suction thrombectomy, catheter-directed thrombolysis and anticoagulation without subsequent oxygen requirement. Three months later, she presented with two weeks of productive cough and hypoxia requiring high flow nasal cannula. CT chest showed worsening native lung fibrosis with ground glass opacities without PE or allograft infiltrate. Bronchoalveolar lavage was negative for infection, recent transbronchial biopsies were negative for rejection, and no donor specific antibodies were identified. Despite empiric antibiotics and pulse dose steroids for native lung exacerbation, she developed worsening hypoxia with progressive native lung infiltrates. A perfusion scan revealed 68% and 32% perfusion to the left and right lung, respectively. A right heart catheterization was performed, showing no intracardiac or pulmonary shunt, a mildly increased gradient across the left pulmonary artery (PA) anastomosis, and a marked improvement in left PA PaO2 during right PA balloon occlusion. On hospital day 16, repeat perfusion scan demonstrated an increase in relative perfusion to the allograft (83%). The patient was discharged on 3L oxygen and remains stable as an outpatient. <h3>Summary</h3> Severe hypoxia in the setting of a functioning SLT during a native lung exacerbation is rare. Literature on normal perfusion after SLT remains limited, with small studies suggesting ∼75% of fractional perfusion to the allograft without native lung exacerbation. Similar cases of inappropriate shunting after SLT had improvement in oxygenation after contralateral PA banding with other options including intravascular interventions or contralateral SLT. Further studies characterizing optimal perfusion after SLT and interventions for inappropriate shunting are needed.

Role of Qualitative and Quantitative Indocyanine Green Angiography to Assess Mastectomy Skin Flaps Perfusion in Nipple/Skin-Sparing and Skin-Reducing Mastectomies with Implant-Based Breast Reconstruction.

Methods Consecutive women scheduled for nipple/skin-sparing/skin-reducing mastectomy between May 2020 and April 2021 were prospectively enrolled. Patients were divided into Group 1 in the absence of superficial and full-thickness necrosis (SN; FTN) and Group 2 in the presence of both. T1 (time between ICG injection and the initial perfusion of the least perfused MSF area), ICG-Q1, and ICG-Q% (absolute and relative perfusion values of the least vascularized area) were collected. Results 38 breasts were considered. FTN was reported in 4 breasts (10.5%) and SN in 3 (7.9%). The two groups statistically differ in T1 (Group2 > Group1) and ICG-Q% (Group1 > Group2) (p < 0.05). T1 could statistically predict ICG-Q1 and ICG-Q%. Both quantitative values have a sensitivity of 57% and a NPV of 89%; ICG-Q% shows higher specificity (81% vs 77%) and PPV (40% vs 36%). Conclusions Quantitative ICG angiography may additionally reduce MSF necrosis. Moreover, longer T1 may indicate possible postoperative necrosis. Considering these factors, intraoperative changes of reconstructive strategy could be adopted to reduce reconstructive failure.

School-age structural and functional MRI and lung function in children following lung resection for congenital lung malformation in infancy

BackgroundThe management of asymptomatic congenital lung malformations is debated. Particularly, there is a lack of information regarding long-term growth and development of the remaining lung in children following lung resection for congenital lung malformations. In addition to conventional pulmonary function tests, we used novel functional magnetic resonance imaging (MRI) methods to measure perfusion and ventilation.ObjectiveTo assess functionality of the remaining lung expanded into the thoracic cavity after resection of congenital lung malformations.Materials and methodsA prospective, cross-sectional pilot study in five children who had surgery for congenital lung malformations during infancy. Participants had structural and functional MRI as well as spirometry, body plethysmography and multiple breath washout at school age.ResultsStructural MRI showed an expansion of the remaining lung in all cases. Fractional ventilation and relative perfusion of the expanded lung were locally decreased in functional MRI. In all other parts of the lungs, fractional ventilation and relative perfusion were normal in all children. There was an association between overall impairment of perfusion and elevated lung clearance index. The results of spirometry and body plethysmography varied between patients, including normal lung function, restriction and obstruction.ConclusionFractional ventilation and relative perfusion maps from functional MRI specifically locate impairment of the remaining lung after lung resection. These changes are not captured by conventional measures such as structural MRI and standard pulmonary function tests. Therefore, following lung resection for congenital lung malformation, children should be investigated more systematically with functional lung MRI.

Human Bone Marrow Mononuclear Cells Do Not Improve Limb Perfusion in the Hindlimb Ischemia Model.

Effective treatments for chronic limb-threatening ischemia are lacking. (Pre)clinical studies on administration of bone marrow (BM) mononuclear cells (MNCs) and BM-derived mesenchymal stromal cells (MSCs) have shown variable results and no studies have directly compared administration of human BM MNCs and BM MSCs in in vivo models. We studied the effect of intramuscular administration of human BM-derived MNCs and MSCs on limb perfusion in the murine hindlimb ischemia (HLI) model. Human BM MNCs and MSCs were obtained from healthy consenting donors. Both cell types were cryopreserved before use. Twenty-four hours after induction of HLI, nude NMRI mice were randomized to receive intramuscular administration of human BM MNCs (n = 13), or BM MSCs (n = 14), or vehicle control (n = 19) in various doses. Limb perfusion was measured using laser Doppler imaging on day 0, 1, 4, 7, 10, and 14. Intramuscular injection of human BM MNCs did not improve limb perfusion as compared with vehicle over the 2 weeks after cell administration (P = 0.88, mean relative perfusion for vehicle 0.56 ± 0.04 and 0.53 ± 0.04 for BM MNCs at day 14). Administration of human BM MSCs significantly improved limb perfusion as compared with both BM MNCs and vehicle (P ≤ 0.001, mean relative perfusion at day 14 0.79 ± 0.06). Our data suggest that BM MNCs are less suitable than BM MSCs for cell-based therapy that aims to restore perfusion.

A preliminary evaluation of a high temporal resolution data-driven motion correction algorithm for rubidium-82 on a SiPM PET-CT system

BackgroundIn myocardial perfusion PET, images are acquired during vasodilator stress, increasing the likelihood of intra-frame motion blurring of the heart in reconstructed static images to assess relative perfusion. This work evaluated a prototype data-driven motion correction (DDMC) algorithm designed specifically for cardiac PET. MethodsA cardiac torso phantom, with a solid defect, was scanned stationary and being manually pulled to-and-fro in the axial direction with a random motion. Non-motion-corrected (NMC) and DDMC images were reconstructed. Total perfusion deficit was measured in the defect and profiles through the cardiac insert were defined. In addition, 46 static perfusion images from 36 rubidium-82 MPI patients were selected based upon a perception of motion blurring in the images. NMC and DDMC images were reconstructed, blinded, and scored on image quality and perceived motion. ResultsPhantom data demonstrated near-perfect recovery of myocardial wall visualization and defect quantification with DDMC compared with the stationary phantom. Quality of clinical images was NMC: 10 non-diagnostic, 31 adequate, and 5 good; DDMC images: 0 non-diagnostic, 6 adequate, and 40 good. ConclusionThe DDMC algorithm shows great promise in rubidium MPI PET with substantial improvements in image quality and the potential to salvage images considered non-diagnostic due to significant motion blurring.

Near-Infrared Fluorescence with Indocyanine Green to Assess Bone Perfusion: A Systematic Review.

Background: Adequate perfusion of a bone flap is essential for successful reconstruction of osseous defects. Unfortunately, complications related to inadequate bone perfusion are common. Near-infrared fluorescence (NIRF) imaging enables intraoperative visualization of perfusion. NIRF has been investigated in reconstructive surgery to aid the surgeon in clinical perioperative assessment of soft tissue perfusion. However, little is known on the beneficial use of NIRF to assess bone perfusion. Therefore, the aim of this review was to search for studies evaluating NIRF to assess bone perfusion. Methods: A systematic review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, was performed. Studies up to October 2021 were included. We extracted data regarding the study population, size and design, reported objective fluorescence parameters and the methodology used for fluorescence imaging and processing. Results: Ten articles were included. Studies reported unevenly on the protocol used for NIRF imaging. Five studies reported objective parameters. Absolute and relative perfusion parameters and parameters derived from maximum fluorescence were reported. The clinical significance of these parameters has not been evaluated in humans. Conclusion: The evidence on bone perfusion as measured with NIRF is limited. More clinical studies are required.

Video demonstrating use of the SPY-PHI QP measuring relative perfusion values in an implant-based breast reconstruction (right breast)

Video demonstrating use of the SPY-PHI QP measuring relative perfusion values in an implant-based breast reconstruction (right breast)

Video demonstrating use of the SPY-PHI QP measuring relative perfusion values in autologous breast reconstructions: illustrated by a deep inferior epigastric artery perfo-rator flap (recording from left side)

Video demonstrating use of the SPY-PHI QP measuring relative perfusion values in autologous breast reconstructions: illustrated by a deep inferior epigastric artery perfo-rator flap (recording from left side)

Video demonstrating use of the SPY-PHI QP measuring relative perfusion values in autologous breast reconstructions: illustrated by a latissimus dorsi muscle flap

Video demonstrating use of the SPY-PHI QP measuring relative perfusion values in autologous breast reconstructions: illustrated by a latissimus dorsi muscle flap

Optimal parametric imaging methods for dual‐time‐window [18F]flutemetamol and [18F]florbetaben PET studies

AbstractBackgroundAccurate quantitative measures of amyloid beta (Aβ) plaques are needed to identify individuals with subthreshold Aβ levels or for measuring small changes over time. To this end, dynamic or dual‐time‐window scanning protocols are required. Optimal pharmacokinetic models for quantifying Aβ burden using both [18F]flutemetamol and [18F]florbetaben dual‐time‐window scans have previously been identified at a region of interest (ROI) level. This study aimed to determine optimal parametric methods for analyses of [18F]flutemetamol and [18F]florbetaben dual‐time‐window scans.MethodForty‐six participants were scanned on a PET/MR scanner using a dual‐time‐window protocol and either [18F]flutemetamol or [18F]florbetaben. The following parametric approaches were used to derive DVR estimates: reference Logan (RLogan), receptor parametric mapping (RPM), two‐step simplified reference tissue model (SRTM2) and multilinear reference tissue models (MRTM0, MRTM1, MRTM2), all with cerebellar grey matter as reference tissue. In addition, a standardized uptake value ratio (SUVR) was calculated for the 90‐110 min post injection interval. All parametric images were assessed visually for possible image artefacts and regional cortical outcome measures were compared with DVR derived using regional RLogan, based on AUC values for differentiating between Aβ‐positive and Aβ‐negative scans, Bland‐Altman plots and linear regression analyses.ResultVisually, RPM and SRTM2 performed best across tracers and, in addition to SUVR, provided the highest AUC values for differentiating between Aβ‐positive and Aβ‐negative scans ([18F]flutemetamol: range AUC=0.96‐0.97, [18F]florbetaben: range AUC=0.83‐0.85). Outcome parameters of most methods were highly correlated with those of the reference method (R2≥0.87), with lowest correlations observed for MRTM2 (R2=0.71‐0.80). Furthermore, bias was low (≤5%) and independent of underlying amyloid burden for MRTM0 and MRTM1. On the other hand, bias in SUVR was high for [18F]flutemetamol (mean bias&gt;10%), but low for [18F]florbetaben (mean bias=1%) and strongly proportional with underlying Aβ burden for both tracers.ConclusionThe best overall compromise was provided by MRTM0, followed closely by SRTM2. SRTM2 is the preferred method for parametric imaging because, in addition to its good performance, it has the advantage of providing a measure of relative perfusion (R1), which is useful for measuring disease progression. “This work has received support from the EU‐EFPIA Innovative Medicines Initiatives 2 Joint Undertaking (grant No 115952).”

Effect of Salbutamol on Lung Ventilation in Children with Cystic Fibrosis: Comprehensive Assessment Using Spirometry, Multiple-Breath Washout, and Functional Lung Magnetic Resonance Imaging

Background: Inhalation therapy is one of the cornerstones of the daily treatment regimen in patients with cystic fibrosis (CF). Recommendations regarding the addition of bronchodilators, especially salbutamol are conflicting due to the lack of evidence. New diagnostic measures such as multiple-breath washout (<underline>MBW)</underline> and functional magnetic resonance imaging (MRI) have the potential to reveal new insights into bronchodilator effects in patients with CF. Objective: The objective of the study was to comprehensively assess the functional response to nebulized inhalation with salbutamol in children with CF. Methods: Thirty children aged 6–18 years with stable CF performed pulmonary function tests, MBW, and matrix pencil-MRI before and after standardized nebulized inhalation of salbutamol. Results: Lung clearance index decreased (improved) by −0.24 turnover (95% confidence interval [CI]: −0.53 to 0.06; p = 0.111). Percentage of the lung volume with impaired fractional ventilation and relative perfusion decreased (improved) by −0.79% (CI: −1.99 to 0.42; p = 0.194) and −1.31% (CI: −2.28 to −0.35; p = 0.009), respectively. Forced expiratory volume (FEV₁) increased (improved) by 0.41 z-score (CI: 0.24–0.58; p < 0.0001). We could not identify specific clinical factors associated with a more pronounced effect of salbutamol. Conclusions: There is a positive short-term effect of bronchodilator inhalation on FEV₁ in patients with CF, which is independent of ventilation inhomogeneity. Heterogeneous response between patients suggests that for prediction of a therapeutic effect this should be tested by spirometry in every patient individually.

Brain structure and perfusion in relation to serum renal function indexes in healthy young adults.

Prior neuroimaging studies of the relationship between the kidney and the brain have been limited to clinical populations and have largely relied on a single modality. We sought to examine the kidney-brain associations in healthy subjects using a combined analysis of multi-modal imaging data. Structural, diffusion, and perfusion magnetic resonance imaging (MRI) scans were performed to measure cortical thickness, white matter integrity, and cerebral blood flow in 157 healthy young adults. Peripheral venous blood samples were collected to measure serum renal function indexes. Correlation analyses were performed to investigate the relations between brain MRI measures and renal function indexes. Results showed that higher serum uric acid level was associated with increased cortical thickness in the transverse temporal gyrus. We also found that decreased serum creatinine level was linked to lower white matter integrity in the sagittal stratum, anterior corona radiata, superior corona radiata, and external capsule. Furthermore, we observed that increased serum uric acid level was related to hyperperfusion in the opercular and triangular parts of inferior frontal gyrus and supramarginal gyrus, and hypoperfusion in the calcarine sulcus, cuneus and lingual gyrus. More importantly, mediation analysis revealed that the relationship between serum uric acid and working memory performance was mediated by perfusion in the supramarginal gyrus and lingual gyrus. These findings not only may extend current knowledge regarding the relationship between the kidney and the brain, but also may inform real-world clinical practice by identification of potential brain regions vulnerable to renal dysfunction.

Imaging Coronary Allograft Vasculopathy with Cardiac PET and Cardiac MRI.

Coronary allograft vasculopathy (CAV) is a leading cause of morbidity and mortality in heart transplant patients. It presents a diagnostic challenge as early CAV is often clinically silent, and it affects both epicardial coronary arteries and microvasculature. This review outlines the role of cardiac positron emission tomography (PET) and cardiac magnetic resonance imaging (CMR) in the diagnosis and prognosis of CAV. Relative myocardial perfusion imaging (MPI) and quantitative myocardial blood flow using cardiac PET are useful in the diagnosis and prognosis of CAV. Late gadolinium enhancement (LGE) and quantitative measures including myocardial perfusion reserve and mean diastolic rate using CMR are useful in the diagnosis and prognosis of CAV. Cardiac PET is now established as a non-invasive imaging modality for screening and monitoring for CAV, and CMR has demonstrated promise in this application. Further investigation of these modalities is needed with larger, multicenter studies that follow patients serially to demonstrate the clinical implications of using these modalities to detect early CAV and alter therapies to improve patient outcomes.

Added value of myocardial blood flow using 18F-flurpiridaz PET to diagnose coronary artery disease: The flurpiridaz 301 trial

Background18F-Flurpiridaz is a promising investigational radiotracer for PET myocardial perfusion imaging with favorable properties for quantification of myocardial blood flow (MBF). We sought to validate the incremental diagnostic value of absolute MBF quantification in a large multicenter trial against quantitative coronary angiography. MethodsWe retrospectively analyzed a subset of patients (N = 231) from the first phase 3 flurpiridaz trial (NCT01347710). Dynamic PET data at rest and pharmacologic stress were fit to a previously validated 2-tissue-compartment model. Absolute MBF and myocardial flow reserve (MFR) were compared with coronary artery disease severity quantified by invasive coronary angiography on a per-patient and per-vessel basis. ResultsStress MBF per-vessel accurately identified obstructive disease (c-index 0.79) and progressively declined with increasing stenosis severity (2.35 ± 0.71 in patients without CAD; 1.92 ± 0.49 in non-obstructed territories of CAD patients; and 1.54 ± 0.50 in diseased territories, P < 0.05). MFR similarly declined with increasing stenosis severity (3.03 ± 0.94; 2.69 ± 0.95; and 2.33 ± 0.86, respectively, P < 0.05). In multivariable logistic regression modeling, stress MBF and MFR provided incremental diagnostic value beyond patient characteristics and relative perfusion analysis. ConclusionsClinical myocardial blood flow measurement with 18F-flurpiridaz cardiac PET shows promise for routine application.