Combined evaluation of regional coronary artery calcium and myocardial perfusion by 82Rb PET/CT in predicting lesion-related outcome

European Journal of Nuclear Medicine and Molecular Imaging - Cardiac imaging with positron emission tomography/computed tomography (PET/CT) allows measurement of coronary artery calcium (CAC),...     

Pathophysiologic correlates of <Superscript>82</Superscript>Rb biodistribution in cardiac PET/CT

Purpose  

PET perfusion imaging with ⁸²Rb is a powerful tool for evaluating coronary artery disease (CAD). Little is known about normal patterns or significance of ⁸²Rb lung distribution in the setting of heart disease. Herein, PET/CT hybrid imaging was used to obtain insights into the frequency and potential radiomorphologic correlates of altered ⁸²Rb distribution.     

Quantification of myocardial blood flow with <Superscript>82</Superscript>Rb dynamic PET imaging

Purpose The PET tracer ⁸²Rb is commonly used to evaluate regional perfusion defects for the diagnosis of coronary artery disease. There is limited information on the quantification of myocardial blood flow and flow reserve with this tracer. The goal of this study was to investigate the use of a one-compartment model of ⁸²Rb kinetics for the quantification of myocardial blood flow. Methods Fourteen healthy volunteers underwent rest and dipyridamole stress imaging with both ¹³N-ammonia and ⁸²Rb within a 2-week interval. Myocardial blood flow was estimated from the time-activity curves measured with ¹³N-ammonia using a standard two-compartment model. The uptake parameter of the one-compartment model was estimated from the time-activity curves measured with ⁸²Rb. To describe the relationship between myocardial blood flow and the uptake parameter, a nonlinear extraction function was fitted to the data. This function was then used to convert estimates of the uptake parameter to flow estimates. The extraction function was validated with an independent data set obtained from 13 subjects with documented evidence of coronary artery disease (CAD). Results The one-compartment model described ⁸²Rb kinetics very well (median R-square = 0.98). The flow estimates obtained with ⁸²Rb were well correlated with those obtained with ¹³N-ammonia (r = 0.85), and the best-fit line did not differ significantly from the identity line. Data obtained from the subjects with CAD confirmed the validity of the estimated extraction function. Conclusion It is possible to obtain accurate estimates of myocardial blood flow and flow reserve with a one-compartment model of ⁸²Rb kinetics and a nonlinear extraction function.     

Incidental extra-cardiac findings on <Superscript>13</Superscript>N-ammonia myocardial perfusion PET/CT

Background

The objective of this study was to describe the prevalence of incidental extra-cardiac findings (IECFs) on myocardial perfusion PET/CTs and the prevalence of potentially clinically relevant and clinically irrelevant IECFs, as well as detection rate of previously unknown malignancies.

Methods and Results

From September 2013 until February 2016, a total of 1397 consecutive patients referred for the evaluation of possible ischemia by ¹³NH₃ PET/CT were prospectively included in a database. IECFs were categorized into three groups: potentially clinically relevant IECFs, IECFs that could potentially cause chest pain, and clinically irrelevant IECFs. Additionally, the prevalence of previously unknown malignancies was determined. In 717 (51%) of these patients, 775 IECFs were reported and 115 IECFs were categorized as potentially clinically relevant in 109 (8%) patients. A total of 145 IECFs that could potentially cause chest pain were detected in 139 (10%) patients and 515 clinically irrelevant IECFs were detected in 469 (34%) of the patients. An unknown primary malignancy was histologically proven in 19 patients (1.4%).

Conclusions

IECFs are detected on myocardial perfusion PET/CT in approximately half of the patients. In the present study, IECFs were potentially clinically relevant in 8% of the patients and in 1.4% an unknown malignancy was found, most of which were lung cancers.

     

Washout of <Superscript>82</Superscript>Rb as a marker of impaired tissue integrity,obtained by list-mode cardiac PET/CT: relationship with perfusion/metabolism patterns of myocardial viability

Purpose  

Myocardial washout of the potassium analogue ⁸²Rb may indicate tissue impairment. Few studies have evaluated its usefulness for viability assessment, and controversial results were reported. We revisited this topic using list-mode positron emission tomography (PET)/CT.     

Comparison of the myocardial blood flow response to regadenoson and dipyridamole: a quantitative analysis in patients referred for clinical <Superscript>82</Superscript>Rb myocardial perfusion PET

Background  

Regadenoson is a novel selective A_2A adenosine receptor agonist, which is administered as an intravenous bolus at a fixed dose. It is currently not clear if the absolute flow increase in response to this fixed dose is a function of distribution volume in individual patients or if it is generally comparable to the previous standard agents dipyridamole or adenosine, which are dosed based on weight. We used quantitative analysis of clinical ⁸²Rb PET/CT studies to obtain further insights.     

Left ventricular mechanical synchrony from stress and rest <Superscript>82</Superscript>Rb PET myocardial perfusion ECG-gated studies: Differentiating normal from LBBB patients

Background  

We have previously reported normal values for LV mechanical synchrony from post-stress exercise ^99mTc SPECT studies; the goal of this study was to develop normal values for mechanical synchrony from pharmacologic stress and rest ⁸²Rb PET studies and compare these values to a population of LBBB patients.     

The effect of time-of-flight and point spread function modeling on <Superscript>82</Superscript>Rb myocardial perfusion imaging of obese patients

Background

The effect of time-of-flight (TOF) and point spread function (PSF) modeling in image reconstruction has not been well studied for cardiac PET. This study assesses their separate and combined influence on ⁸²Rb myocardial perfusion imaging in obese patients.

Methods

Thirty-six obese patients underwent rest-stress ⁸²Rb cardiac PET. Images were reconstructed with and without TOF and PSF modeling. Perfusion was quantitatively compared using the AHA 17-segment model for patients grouped by BMI, cross-sectional body area in the scanner field of view, gender, and left ventricular myocardial volume. Summed rest scores (SRS), summed stress scores (SSS), and summed difference scores (SDS) were compared.

Results

TOF improved polar map visual uniformity and increased septal wall perfusion by up to 10%. This increase was greater for larger patients, more evident for patients grouped by cross-sectional area than by BMI, and more prominent for females. PSF modeling increased perfusion by about 1.5% in all cardiac segments. TOF modeling generally decreased SRS and SSS with significant decreases between 2.4 and 3.0 (P?<?.05), which could affect risk stratification; SDS remained about the same. With PSF modeling, SRS, SSS, and SDS were largely unchanged.

Conclusion

TOF and PSF modeling affect regional and global perfusion, SRS, and SSS. Clinicians should consider these effects and gender-dependent differences when interpreting ⁸²Rb perfusion studies.

     

<Superscript>11</Superscript>C-methionine PET/CT findings in benign brain disease

¹¹C-methionine (MET) is one of the most commonly used positron emission tomography (PET) tracers for evaluation of malignant brain tumor, with MET-PET being a sensitive technique for visualization of primary and recurrent malignant brain tumors. However, previous reports have demonstrated MET uptake in lesions associated with benign brain diseases. These diseases usually show an increase in MET uptake similar to that of malignant tumors. This pitfall in MET-PET image interpretation is important not only for nuclear medicine professionals, but also for radiologists. In this review, we demonstrate the imaging characteristics of MET uptake in benign brain disease, and recommend physician interpretation of imaging findings and disease characteristics for optimal patient management. Benign uptake must be identified to prevent misdiagnosis and unnecessary surgical operations.     

Low-dose dynamic myocardial perfusion imaging by CZT-SPECT in the identification of obstructive coronary artery disease

European Journal of Nuclear Medicine and Molecular Imaging - We measured myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) by a dynamic low-dose CZT-SPECT protocol in patients with...     

Treatment response evaluation with <Superscript>18</Superscript>F-FDG PET/CT and <Superscript>18</Superscript>F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Aim

The aim of this study was to assess the combined use of the radiotracers ¹⁸F-FDG and ¹⁸F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).

Patients and methods

Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with ¹⁸F-FDG and ¹⁸F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, ¹⁸F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, ¹⁸F-FDG PET/CT-based treatment response revealed CR in 14 patients (¹⁸F-FDG PET/CT CR), PR in 11 patients (¹⁸F-FDG PET/CT PR) and progressive disease in four patients (¹⁸F-FDG PET/CT PD). In terms of ¹⁸F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, ¹⁸F-NaF PET/CT depicted 56 of the 129 ¹⁸F-FDG positive lesions (43 %). Follow-up ¹⁸F-NaF PET/CT showed persistence of 81.5 % of the baseline ¹⁸F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to ¹⁸F-FDG negative. Treatment response according to ¹⁸F-NaF PET/CT revealed CR in one patient (¹⁸F-NaF PET/CT CR), PR in five patients (¹⁸F-NaF PET/CT PR), SD in 12 patients (¹⁸F-NaF PET/CT SD), and PD in seven patients (¹⁸F-NaF PET/CT PD). Dynamic ¹⁸F-FDG and ¹⁸F-NaF PET/CT studies showed that SUV_average, SUV_max, as well as the kinetic parameters K₁, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p?<?0.001).

Conclusion

F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of ¹⁸F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, ¹⁸F-NaF PET/CT does not seem to add significantly to ¹⁸F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.

     

Optimization of temporal sampling for <Superscript>82</Superscript>rubidium PET myocardial blood flow quantification

Background

Suboptimal temporal sampling of left ventricular (LV) blood pool and tissue time-activity curves (TACs) may introduce bias and increased variability in estimates of myocardial blood flow (MBF) and flow reserve (MFR) from dynamic PET myocardial perfusion images. We aimed to optimize temporal sampling for estimation of MBF and MFR.

Methods

Twenty-four normal volunteers and 32 patients underwent dynamic stress/rest rubidium-82 chloride (⁸²Rb) PET imaging. Fine temporal sampling was used to estimate the full width at half maximum (FWHM) of the LV blood pool TAC. Fourier analysis was used to determine the longest sampling interval, T _S, as a function of FWHM, which preserved the information content of the blood phase. Dynamic datasets were reconstructed with frame durations varying from 2 to 20 seconds over the first 2 minutes for the blood phase and 30 to 120 seconds for the tissue phase. The LV blood pool and tissue TACs were sampled using regions of interest (ROI) and fit to a compartment model for quantification of MBF and MFR. The effects of temporal sampling on MBF and MFR were evaluated using clinical data and simulations.

Results

T _S increased linearly with input function FWHM (R = 0.93). Increasing the blood phase frame duration from 5 to 15 seconds resulted in MBF and MFR biases of 6-12% and increased variability of 14-24%. Frame durations <5 seconds had biases of less than 5% for both MBF and MFR values. Increasing the tissue phase frame durations from 30 to 120 seconds resulted in <5% biases.

Conclusions

A two-phase framing of dynamic ⁸²Rb PET images with frame durations of 5 seconds (blood phase) and 120 seconds (tissue phase) optimally samples the blood pool TAC for modern 3D PET systems.

     

Relationship between collateral circulation and myocardial viability of <Superscript>18</Superscript>F-FDG PET/CT subtended by chronic total occluded coronary arteries

Objective

To analyze the relationship between the collateral flow of coronary chronic total occlusion (CTO) and myocardial viability detected by ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging.

Methods

A prospective analysis of 104 patients diagnosed by coronary angiography. All patients underwent resting myocardial perfusion imaging and PET/CT within 1 week. The collateral circulation was graded with Rentrop classification as no or poor collateral circulation in 16 CTO vessels, moderate collateral circulation in 34 CTO vessels, and good collateral circulation in 69 CTO vessels. Myocardial viability was determined with myocardial perfusion imaging and PET. The patterns were interpreted as mismatch, match and normal perfusion and ¹⁸F-FDG uptake.

Results

There was no significant correlation between the severity and extent of perfusion defect, myocardial viability and collateral circulation grade. The myocardial viability was normal in mild and moderate hypokinetic regions and decreased in severe hypokinetic and akinesis–dyskinesis regions. The presence of collateral circulation was a sensitive (89%) but not a specific (31%) sign of myocardial viability.

Conclusions

In patients with CTO, collateral circulation does not seem to be an effective way for predicting myocardial viability. Further analysis of PET patterns of viable myocardium is needed to guide further revascularization and predict functional improvement and survival benefit.

     

<Superscript>68</Superscript>Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer

Purpose

The aims of this retrospective analysis were to compare ⁶⁸Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative ⁶⁸Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases.

Methods

In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with ⁶⁸Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05.

Results

In total, 168 ⁶⁸Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both ⁶⁸Ga-PSMA PET-positive and CT-positive, 65 were only ⁶⁸Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more ⁶⁸Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several ⁶⁸Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV_average and SUV_max), its transport rate from plasma to the interstitial/intracellular compartment (K₁), its rate of binding to the PSMA receptor and its internalization (k₃), its influx rate (K_i), and its distribution heterogeneity.

Conclusion

⁶⁸Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. ⁶⁸Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several ⁶⁸Ga-PSMA PET parameters.

     

<Superscript>13</Superscript>N-ammonia myocardial perfusion imaging with a PET/CT scanner: impact on clinical decision making and cost-effectiveness

Purpose The purpose of the study is to determine the impact of ¹³N-ammonia positron emission tomography (PET) myocardial perfusion imaging (MPI) on clinical decision making and its cost-effectiveness. Materials and methods One hundred consecutive patients (28 women, 72 men; mean age 60.9 ± 12.0 years; range 24–85 years) underwent ¹³N-ammonia PET scanning (and computed tomography, used only for attenuation correction) to assess myocardial perfusion in patients with known (n = 79) or suspected (n = 8) coronary artery disease (CAD), or for suspected small-vessel disease (SVD; n = 13). Before PET, the referring physician was asked to determine patient treatment if PET would not be available. Four weeks later, PET patient management was reassessed for each patient individually. Results Before PET management strategies would have been: diagnostic angiography (62 of 100 patients), diagnostic angiography and percutaneous coronary intervention (PCI; 6 of 100), coronary artery bypass grafting (CABG; 3 of 100), transplantation (1 of 100), or conservative medical treatment (28 of 100). After PET scanning, treatment strategies were altered in 78 patients leading to: diagnostic angiography (0 of 100), PCI (20 of 100), CABG (3 of 100), transplantation (1 of 100), or conservative medical treatment (76 of 100). Patient management followed the recommendations of PET findings in 97% of the cases. Cost-effectiveness analysis revealed lower costs of €206/patient as a result of PET scanning. Conclusion In a population with a high prevalence of known CAD, PET is cost-effective and has an important impact on patient management. P.T. Siegrist and L. Husmann contributed equally to this work.