The evaluation of left ventricular dyssynchrony in hypertensive patients with a preserved systolic function undergoing gated SPECT myocardial perfusion imaging

Abstract

Background

Hypertension as a known risk factor for cardiovascular diseases can result in left ventricular dyssynchrony (LVD) leading to uncoordinated contraction. The aim of our study was to evaluate whether systolic mechanical dyssynchrony measured by phase analysis of gated single-photon emission computed tomography (SPECT) imaging occurs in hypertensive patients with a low risk for coronary artery disease and a normal ejection fraction and its possible relationships with severity of hypertension and the influence of antihypertensive treatments.

Methods

A total of 466 patients (328 females and 138 males, with a mean age of 59.62 ± 10.27 years) who had a low risk factor for coronary artery disease, a normal perfusion study and, a normal ejection fraction were included of which 408 was hypertensive and 58 normotensive. Phase analysis parameters (derived using QGS software) were compared in patients with and without hypertension. Using different statistical methods, relationship between derived phase analysis indices (PSD, PHB) for LVD and amount of blood pressure and antihypertensive drugs consumption were evaluated.

Results

The prevalence of LVD in patients with hypertension was 63.2% (n = 258), while it was 6.9% in the normotensive group. The mean values of PSD and PHB were higher in hypertensive patients than normotensive ones (12.55 vs. 5.8 and 39.24 vs. 21.12), respectively, so that, statistically significant differences were found between the patients with and without hypertension (p < 0.001). Furthermore, there was a clear relationship between the severity of hypertension and the degree of LVD: by increasing 1 mmHg in systolic and diastolic blood pressure, PSD and PHB increase by (0.034, 0.108 and 0.035, 0.0311), respectively. The statistical results showed that the frequency of LVD in controlled hypertensive patients taking antihypertensive drugs was 55.2%, which significantly lower compared to the patient suffering from hypertension without taking any hypertensive drug (81.35%, p < 0.001).

Conclusion

Our study findings are in favor of using phase analysis-gated SPECT imaging as a routine way for detection of LVD—known indicator of progression toward systolic dysfunction in the future—in hypertensive patients with a low risk for coronary artery diseases and a normal cardiac systolic function.

From the respective expert viewpoints of the ANM specialty editors

Abstract

Although it may not be well known, the Annals of Nuclear Medicine (ANM) Editorial Committee includes one specialty editor of nuclear medicine physics, one of nuclear medicine technology, one of molecular imaging, and two of radiopharmacology. In addition, a statistics editor and a language editor are also on the committee. Manuscripts submitted to ANM can be peer-reviewed by such specialty editors similar to those submitted to highly ranked journals, which is a great pride and joy to us. To offer our readers a condensed global view on the high-quality research work in the field of nuclear medicine, we have published a mini-review article every year under the joint authorship of the ANM associate editors since 2016. This is our fourth serial review article written by the ANM specialty editors from their respective expert viewpoints.

Total metabolic tumor volume by 18F-FDG PET/CT for the prediction of outcome in patients with non-small cell lung cancer

Abstract

Objective

Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are imaging parameters derived from 18F-FDG PET/CT that have been proposed for risk stratification of cancer patients. The aim of our study was to test whether these whole-body volumetric imaging parameters may predict outcome in patients with non-small cell lung cancer (NSCLC).

Methods

Sixty-five patients (45 men, 20 women; mean age ± SD, 65 ± 12 years), with histologically proven NSCLC who had undergone 18F-FDG PET/CT scan before any therapy, were included in the study. Imaging parameters including SUV_max, SUV_mean, total MTV (MTV_TOT) and whole-body TLG (TLG_WB) were determined. Univariate and multivariate analyses of clinical and imaging variables were performed using Cox proportional hazards regression. Survival analysis was performed using Kaplan–Meier method and log-rank tests.

Results

A total of 298 lesions were analyzed including 65 primary tumors, 114 metastatic lymph nodes and 119 distant metastases. MTV_TOT and TLG_WB could be determined in 276 lesions. Mean value of MTV_TOT was 81.83 ml ± 14.63 ml (SE) whereas mean value of TLG_WB was 459.88 g ± 77.02 g (SE). Univariate analysis showed that, among the variables tested, primary tumor diameter (p = 0.0470), MTV of primary tumor (p = 0.0299), stage (p < 0.0001), treatment (p < 0.0001), MTV_TOT (p = 0.0003) and TLG_WB (p = 0.0002) predicted progression-free survival in NSCLC patients, while age (p = 0.0550), MTV of primary tumor (p = 0.0375), stage (p < 0.0001), treatment (p < 0.0001), MTV_TOT (p = 0.0001) and TLG_WB (p = 0.0008) predicted overall survival. At multivariate analysis age, TLG_WB and stage were retained in the model for prediction of progression-free survival (p < 0.0001), while age, MTV_TOT and stage were retained in the model for prediction of overall survival (p < 0.0001). Survival analysis showed that patients with TLG_WB ≤ 54.7 g had a significantly prolonged progression-free survival as compared to patients with TLG_WB > 54.7 g (p < 0.0001). Moreover, overall survival was significantly better in patients showing a MTV_TOT ≤ 9.5 ml as compared to those having MTV_TOT > 9.5 ml (p < 0.0001). Similar results were obtained in a subgroup of 43 patients with advanced disease (stages III and IV).

Conclusions

Whole-body PET-based volumetric imaging parameters are able to predict outcome in NSCLC patients.

Correction of head movement by frame-to-frame image realignment for receptor imaging in positron emission tomography studies with [ 11 C]raclopride and [ 11 C]FLB 457

Abstract

Objective

Positron emission tomography (PET) scans of imaging receptors require 60–90-min dynamic acquisition for quantitative analysis. Head movement is often observed during scanning, which hampers the reliable estimation of quantitative parameters. This study evaluated image-based motion correction by frame-to-frame realignment for PET studies with [¹¹C]raclopride and [¹¹C]FLB 457 acquired by an Eminence SET-3000GCT/X and investigated the effect of this correction on the quantitative outcomes.

Methods

First, an optimal method for estimating motion parameters was evaluated by computer simulation. Simulated emission sinograms were reconstructed to the PET images with or without attenuation correction using a µ-map of the transmission scan. Six motion parameters were estimated frame-by-frame by registering each frame of the PET images to several types of reference images and the reliability of registration was compared. Next, in [¹¹C]raclopride and [¹¹C]FLB 457 studies in normal volunteers, six motion parameters for each frame were estimated by the registration method determined from the simulation results. Head movement was corrected by realigning the PET images reconstructed with a motion-included µ-map in which a mismatch between the transmission and emission scans was corrected. After this correction, time-activity curves (TAC) for the striatum or cerebral cortex were obtained and the binding potentials of the receptors (BP_ND) were estimated using the simplified reference tissue model.

Results

In the simulations, the motion parameters could be reliably estimated by registering each frame of the non-attenuation-corrected PET images to their early-phase frame. The motion parameters in the human studies were also obtained using the same method. After correction, a discontinuity of TACs in the striatum and cerebral cortex was remarkably improved and the BP_ND values in these regions increased. Compared to the motion-corrected PET images reconstructed using the measured µ-map, the images reconstructed using the motion-included µ-map did not result in a remarkable improvement of BP_ND in the striatum of [¹¹C]raclopride studies, while the BP_ND in the cerebral cortex changed in some [¹¹C]FLB 457 studies in which large head movement was observed.

Conclusions

In PET receptor imaging, head movement during dynamic scans can be corrected by frame-to-frame realignment. This method is easily applicable to clinical studies and provides reliable TACs and BP_ND.

PSMA SPECT/CT with 99m Tc-MIP-1404 in biochemical recurrence of prostate cancer: predictive factors and efficacy for the detection of PSMA-positive lesions at low and very-low PSA levels

Abstract

Background

The in vivo expression of the prostate-specific membrane antigen (PSMA) can be investigated using the SPECT-suitable tracer ^99mTc-MIP-1404. We investigated the performance of ^99mTc-MIP-1404 PSMA SPECT/CT in the detection of PSMA-positive tumor lesions in patients suffering from biochemical recurrence of prostate cancer presenting with serum levels of the prostate-specific antigen (PSA) below 1 ng/mL.

Methods

We retrospectively analyzed ^99mTc-MIP-1404-SPECT/CT scans

of 50 patients (25 with low PSA levels between > 0.5 and 1 ng/mL and 25 with very low PSA levels between 0.2 and 0.5 ng/mL) that had undergone whole-body planar scintigraphy and SPECT/CT of the thorax, abdomen and pelvis 3–4 h p.i. of 691 ± 72 MBq ^99mTc-MIP-1404. All datasets were evaluated for the presence and location of PSMA-positive tumor lesions, in which maximal standardized uptake values (SUV_max) were also measured. Based on the results of the quantitative evaluation as well as on biochemical and histological parameters, predictive factors for a positive ^99mTc-MIP-1404 scan result were determined. The influence of ^99mTc-MIP-1404 PSMA SPECT/CT on further therapy planning was assessed, based on the decision-making of the interdisciplinary tumor board.

Results

Pathological ^99mTc-MIP-1404 uptake was detected in a total of 25 patients (50%). In the very low PSA subgroup, detection rates of PSMA-positive lesions suggestive of tumor recurrence were 44%, in the low-PSA subgroup 56%. Gleason scores ≥ 8 and the presence of antiandrogen deprivation therapy were further significant predictors of pathological ^99mTc-MIP-1404 uptake. This was paralleled by significantly higher lesional SUV_max patients with PSA levels > 0.5 ng/mL and Gleason scores ≥ 8 compared to those without these two features. Changes in therapeutic strategy following MIP-1404 imaging were recommended by the interdisciplinary tumor board in 25/50 of patients.

Conclusion

^99mTc-MIP-1404 PSMA-SPECT/CT demonstrated a high performance in detecting PSMA-positive lesions suggestive of tumor recurrence in patients with biochemical recurrence of prostate cancer and low and very low serum PSA levels. Results from MIP-1404 PSMA SPECT/CT have therapeutic impact in one-half of the patients examined by this technology.

Association between carotid 18 F-NaF and 18 F-FDG uptake on PET/CT with ischemic vascular brain disease on MRI in patients with carotid artery disease

Abstract

Objective

Atherosclerosis is a dynamic and complex process characterized by the formation and progression of plaque mediated by various pathophysiologic steps including inflammation and calcification. The present study aimed to evaluate the association between carotid ¹⁸F-sodium fluoride (NaF) and ¹⁸F-fluorodeoxyglucose (FDG) uptake with the severity of ischemic vascular brain disease on MRI in patients with carotid artery disease.

Methods

A total of 28 patients who were scheduled to undergo clinically indicated carotid endarterectomy or stenting for carotid artery disease were examined with ¹⁸F-NaF and ¹⁸F-FDG PET/CT and brain MRI. The PET/CT images were evaluated by qualitative and semiquantitative analyses. The maximum standardized uptake value (SUV) for the plaque and the average of mean SUV within the lumen of both internal jugular veins was calculated, and the target-to-blood pool ratio (TBR) was determined. The ischemic vascular brain disease on MRI was graded separately in the bilateral hemisphere as 0, 1, 2, and 3, with 0 being absent and 3 being the most severe.

Results

In two patients, only a unilateral carotid artery was analyzed because of previous indwelling stent. ¹⁸F-NaF focal uptake was observed in 50 carotid arteries. ¹⁸F-FDG focal uptake was observed in 47 carotid arteries. The mean (± SD) ¹⁸F-NaF TBR (2.93 ± 0.89) was significantly higher than the mean (± SD) ¹⁸F-FDG TBR (2.41 ± 0.84) (p < 0.001). The mean (± SD) values of ¹⁸F-NaF TBR were 2.63 ± 0.76 in grade 1, 2.90 ± 0.91 in grade 2, and 3.81 ± 0.60 in grade 3. Significant differences in ¹⁸F-NaF TBR were observed between grades 1 and 3 (p < 0.001) and grades 2 and 3 (p = 0.02). The mean (± SD) values of ¹⁸F-FDG TBR were 2.35 ± 0.77 in grade 1, 2.23 ± 0.48 in grade 2, and 2.87 ± 1.32 in grade 3. No significant differences in ¹⁸F-FDG TBR were noted between any of the ischemic vascular brain disease grades.

Conclusions

These preliminary results suggest that carotid ¹⁸F-NaF uptake in patients with carotid artery disease may be associated with the severity of the ischemic vascular brain disease observed on MRI.

Potential prognostic implications of myocardial thallium-201 and iodine-123-beta-methylpentadecanoic acid dual scintigraphy in patients with Anderson–Fabry disease

Abstract

Objectives

Information on the relationship between myocardial damage assessed by myocardial scintigraphy and prognosis in patients with Anderson–Fabry disease (AFD) is lacking. We therefore aimed to investigate the prognostic impacts of myocardial thallium-201 (²⁰¹Tl) and iodine-123 beta-methyl 15-para-iodophenyl 3(R, S)-methylpentadecanoic acid (¹²³I-BMIPP) dual scintigraphy in patients with AFD.

Methods

Eighteen consecutive patients with AFD underwent resting myocardial ²⁰¹Tl/¹²³I-BMIPP dual scintigraphy. Total defect scores (TDS) on both images were calculated visually according to the 17-segment model using a 5-point scoring system. The mismatch score (MS) was calculated as ‘TDS on ¹²³I-BMIPP—TDS on ²⁰¹Tl’.

Results

Six major adverse cardiac events (MACEs) were recorded during a mean follow-up of 6.7 ± 4.2 years (three heart failure requiring hospitalization and three cardiac deaths). Left ventricular mass index, left atrial diameter, brain natriuretic peptide, TDS on ¹²³I-BMIPP, and MS were all significantly greater in patients with MACEs compared with those without. Kaplan–Meier analysis indicated that high TDS on ¹²³I-BMIPP and high MS were associated with poor event-free survival.

Conclusion

TDS on ¹²³I-BMIPP was a better prognostic determinant in patients with AFD than TDS on ²⁰¹Tl. Myocardial ²⁰¹Tl/¹²³I-BMIPP dual scintigraphy may thus be a useful noninvasive modality for evaluating prognosis in patients with AFD.

Comparisons of 131 I-rituximab treatment responses in patients with aggressive lymphoma and indolent lymphoma

Abstract

Objective

We evaluated the changes in treatment response over time after single ¹³¹I-rituximab radioimmunotherapy (RIT) according to non-Hodgkin lymphoma (NHL) types.

Methods

Fifteen aggressive and 21 indolent lymphoma cases undergoing RIT were evaluated. All patients underwent ¹⁸F-FDG-PET-CT before and 5 days, 1, and 3 months after RIT. The maximum standardized uptake value (SUV) and the sum of the products of the longest perpendicular diameters of tumours (SPD) were evaluated. Treatment responses were evaluated 1 and 3 months after RIT

Results

In aggressive lymphoma, SUV decreased at 5 days after RIT but increased after that. SPD decreased at 1 month but significantly increased at 3 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) at 1 month after RIT were changed to PD at 3 months after RIT. In indolent lymphoma, the SUV decreased continuously until 1 month after RIT. The SPD significantly decreased at 1 month and tended to further decrease to 3 months. CR, PR, SD, and PD at 1 month after RIT were achieved in 0, 8, 13, and 0 cases, respectively. Among the 13 SD cases, one changed to CR, three changed to PR, and nine had not changed at 3 months after RIT.

Conclusions

The treatment response to single RIT differed depending on NHL type. These findings suggest a need to establish an optimal treatment regimen based on NHL aggressiveness.

Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients

Abstract

Objective

To investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on positron emission tomography–computed tomography (PET/CT) and the response to treatment following the start of enzalutamide or abiraterone in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods

All consecutive ⁶⁸Ga-PSMA-11 PET/CT scans routinely performed at our institution during more than 4 years were retrospectively screened for inclusion. We included mCRPC patients with a baseline PSMA PET/CT performed less than 2 months before the start of either enzalutamide or abiraterone, and a follow-up PSMA PET/CT performed no more than a year after, while still under those novel antiandrogen drugs (NAD). The associated clinical records were reviewed. Patients were considered treatment responders if they presented decreasing PSA levels > 50% or a radiological response based on RECIST 1.1 criteria. PSMA expression changes on the follow-up PET/CT were assessed using per-patient dominant response criteria to classify patients as PSMA-responders (complete disappearance of pathologic PSMA uptake, or a decreased uptake of the majority of lesions) or PSMA-non-responders (new PSMA-expressing lesions, increased uptake of the majority of lesions, or stable PSMA expression of the disease). Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated.

Results

A total of 11 and 15 patients were included in the enzalutamide and abiraterone groups. Median follow-up was 110 (IQR 76–124) and 87 (IQR 71–242) days, respectively. All treatment responders (3 enzalutamide and 4 abiraterone) were considered PSMA-responders, and all treatment non-responders (8 enzalutamide, 11 abiraterone) were considered PSMA-non-responders. PSMA PET response was thus perfectly associated with conventional response criteria (p = 0.006, Phi = 1 for enzalutamide; p = 0.001, Phi = 1 for abiraterone). In our cohort, no PSMA expression flare phenomenon was detected on follow-up PET/CT scans at a median follow-up of 3 months. However, an early and short-lived flare cannot be excluded.

Conclusions

This retrospective study suggests that, after a median follow-up of 3 months under enzalutamide or abiraterone, PSMA expression changes on PET/CT are strongly associated with response to treatment. Prospective studies are needed to better understand PSMA expression dynamics following the start of enzalutamide and abiraterone, along with the role of PSMA PET/CT in response assessment.