Accuracy of holmium-166 SPECT/CT quantification over a large range of activities

Background: Quantitative imaging is a crucial step for dosimetry in radionuclide therapies. Traditionally, SPECT/CT imaging is quantified based on scanner-specific conversion factors or self-calibration, but recently absolute quantification methods have been introduced in commercial SPECT reconstruction software (Broad Quantification, Siemens Healthineers). In this phantom study we investigate the accuracy of three quantification methods for holmium-166 SPECT/CT imaging, and provide recommendations for clinical dosimetry.Methods: One cylindrical phantom, filled with a homogeneous holmium-166-chloride activity concentration solution, was imaged at one time point to determine a scanner-specific conversion factor, and to characterize the spatial dependency of the activity concentration recovery. One Jaszczak phantom with six fillable spheres, 10:1 sphere-to-background ratio, was imaged over a large range of holmium-166 activities (61-3130 MBq). The images were reconstructed with either an ordered subset expectation maximization (OSEM, Flash3D-reconstruction; scanner-specific quantification or self-calibration quantification) or an ordered subset conjugate gradient (OSCG, xSPECT-reconstruction; Broad Quantification) algorithm. These three quantification methods were compared for the data of the Jaszczak phantom and evaluated based on whole phantom recovered activity, activity concentration recovery coefficients (ACRC), and recovery curves. Results: The activity recovery in the Jaszczak phantom was 28–115% for the scanner-specific, and 57–97% for the Broad Quantification quantification methods, respectively. The self-calibration-based activity recovery is inherently always 100%. The ACRC for the largest sphere (Ø60 mm, ~ 113 mL) ranged over (depending on the activity level) 0.22–0.89, 0.76–0.86, 0.39–0.72 for scanner-specific, self-calibration and Broad Quantification, respectively. Conclusion: Of the three investigated quantification methods, the self-calibration technique produces quantitative SPECT images with the highest accuracy in the investigated holmium-166 activity range.</p

Cardiac Abnormalities in Individuals Aged ≥ 50 Years with Severe Obesity Referred for Bariatric Surgery

(Figure presented.)</p

Cardiac Abnormalities in Individuals Aged ≥ 50 Years with Severe Obesity Referred for Bariatric Surgery

(Figure presented.)</p

Epicardial adipose tissue and pericardial constraint in heart failure with preserved ejection fraction

AIMS: Obesity and epicardial adiposity play a role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), and both are associated with increased filling pressures and reduced exercise capacity. The haemodynamic basis for these observations remains inaccurately defined. We hypothesize that an abundance of epicardial adipose tissue (EAT) within the pericardial sac is associated with haemodynamic signs of pericardial constraint.METHODS AND RESULTS: HFpEF patients who underwent invasive heart catheterization with simultaneous echocardiography were included. Right atrial pressure (RAP), right ventricular end-diastolic pressure, and pulmonary capillary wedge pressure (PCWP) were invasively measured. The presence of a square root sign on the right ventricular pressure waveform and the RAP/PCWP ratio (surrogate parameters for pericardial constraint) were investigated. EAT thickness alongside the right ventricle was measured on echocardiography. Sixty-four patients were studied, with a mean age of 73 ± 10 years, 64% women, and a mean body mass index (BMI) of 28.6 ± 5.4 kg/m 2 . In total, 47 patients (73%) had a square root sign. The presence of a square root sign was associated with higher BMI (29.3 vs. 26.7 kg/m 2 , P = 0.02), higher EAT (4.0 vs. 3.4 mm, P = 0.03), and higher RAP (9 vs. 6 mmHg, P = 0.04). Women had more EAT than men (4.1 vs. 3.5 mm, P = 0.04), despite a comparable BMI. Women with a square root sign had significantly higher EAT (4.3 vs. 3.3 mm, P = 0.02), a higher mean RAP (9 vs. 5 mmHg, P = 0.02), and a higher RAP/PCWP ratio (0.52 vs. 0.26, P = 0.002). In men, such associations were not seen, although there was no significant interaction between men and women (P &gt; 0.05 for all analyses). CONCLUSIONS: Obesity and epicardial adiposity are associated with haemodynamic signs of pericardial constraint in patients with HFpEF. The pathophysiological and therapeutic implications of this finding need further study.</p

A Clinical Feasibility Study To Image Angiogenesis in Patients With Arteriovenous Malformations Using 68Ga-RGD PET/CT

Objective: Arteriovenous Malformations (AVMs) have an inherent capacity to form new blood vessels resulting in excessive lesion growth and this is further triggered by the release of angiogenic factors. Gallium-68 (68Ga) labeled arginine-glycine-aspartate tripeptide sequence (RGD) positron emission tomography (PET)/computed tomography (CT) imaging (68Ga-RGD PET/CT) may provide insight in the angiogenic status and treatment response of AVMs. This clinical feasibility study demonstrates that 68Ga-RGD PET/CT imaging can be used to quantitatively assess angiogenesis in peripheral AVMs. Methods: Ten patients with a peripheral AVM (mean age 40 years, four men, six women) and scheduled for endovascular embolization treatment, were prospectively included. All patients underwent 68Ga-RGD PET/CT imaging 60 min after injection (mean dose 207±5 MBq). Radiotracer uptake in AVM, blood-pool, and muscle activity were quantified as Standardized Uptake Values (SUVmax, SUVpeak) and descriptive analysis of the PET/CT images was performed. Furthermore, immunohistochemical analysis was performed on surgical biopsy material of peripheral AVMs to investigate the expression pattern of integrin αvβ3.Results: 68Ga-RGD PET/CT imaging showed enhanced radiotracer uptake in all AVM lesions (mean SUVmax 3.0±1.1; mean SUVpeak 2.2±0.9). Lesion/blood and lesion/muscle ratios were 3.5±2.2 and 4.6±2.8, respectively. Radiotracer uptake in AVMs was significantly higher compared to uptake in background tissue (p=0.0006 and p=0.0014) for blood and muscle, respectively. Initial observations include identification of radiotracer uptake in (multifocal) AVM lesions and enhanced radiotracer uptake in intra-osseous components in those AVM cases affecting the bone integrity. Immunohistochemical analysis revealed cytoplasmatic and cell membranous integrin αvβ3 expression in endothelial cells of AVMs. Conclusion: This feasibility study showed increased radiotracer uptake in AVM with angiogenic activity compared to surrounding tissue without angiogenic activity, suggesting that 68Ga-RGD PET/CT imaging can be used as a tool to quantitatively determine angiogenesis in AVM. Further studies will be conducted to explore the potential of 68Ga-RGD PET/CT imaging for guiding current treatment decisions and for assessment of response to anti-angiogenic treatment

Contralateral Regional Recurrence in Lateralized or Paramedian Early-Stage Oral Cancer Undergoing Sentinel Lymph Node Biopsy-Comparison to a Historic Elective Neck Dissection Cohort

Introduction: Nowadays, two strategies are available for the management of the clinically negative neck in early-stage (cT1-2N0) oral squamous cell carcinoma (OSCC): elective neck dissection (END) and sentinel lymph node biopsy (SLNB). SLNB stages both the ipsilateral and the contralateral neck in early-stage OSCC patients, whereas the contralateral neck is generally not addressed by END in early-stage OSCC not involving the midline. This study compares both incidence and hazard of contralateral regional recurrences (CRR) in those patients who underwent END or SLNB. Materials and Methods: A retrospective multicenter cohort study, including 816 lateralized or paramedian early-stage OSCC patients, staged by either unilateral or bilateral END (n = 365) or SLNB (n = 451). Results: The overall rate of occult contralateral nodal metastasis was 3.7% (30/816); the incidence of CRR was 2.5% (20/816). Patients who underwent END developed CRR during follow-up more often than those who underwent SLNB (3.8 vs. 1.3%; p = 0.018). Moreover, END patients had a higher hazard for developing CRR than SLNB patients (HR = 2.585; p = 0.030). In addition, tumor depth of invasion was predictive for developing CRR (HR = 1.922; p = 0.009). Five-year disease-specific survival in patients with CRR was poor (42%) compared to patients in whom occult contralateral nodal metastases were detected by SLNB or bilateral END (88%), although not statistically different (p = 0.066). Conclusion: Our data suggest that SLNB allows for better control of the contralateral clinically negative neck in patients with lateralized or paramedian early-stage OSCC, compared to END as performed in a clinical setting. The prognosis of those in whom occult contralateral nodal metastases are detected at an earlier stage may be favorable compared to those who eventually develop CRR, which highlights the importance of adequate staging of the contralateral clinically negative neck

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [⁶⁸Ga]Ga-DOTA-E-[c(RGDfK)]₂ PET/CT

Purpose: Angiogenesis plays an important role in the growth and metastatic spread of solid tumours and is characterised by the expression of integrins on the cell surface of endothelial cells. Radiolabelled RGD peptides specifically target angiogenesis-related αvβ3 integrins, expressed on the activated endothelial cells of sprouting blood vessels. Here, we investigated the potential of 68Ga[Ga]-DOTA-E-[c(RGDfK)]2 (68Ga-RGD) PET/CT imaging to visualise angiogenesis in patients with Oral Squamous Cell Carcinoma (OSCC). Methods: Ten patients with OSCC and scheduled for surgical resection including elective neck dissection, received an intravenously administration of 68Ga-RGD (42±8 µg; 214±9 MBq). All patients subsequently underwent dynamic (n=5) or static PET/CT imaging (n=5) for 60 minutes or for 4 min/bed position at 30, 60, and 90 minutes after injection, respectively. Quantitative tracer uptake in tumour lesions was expressed as Standardised Uptake Values (SUV). Additionally, tumour tissue was immunohistochemically stained for αvβ3 integrin to assess the expression pattern. Results: 68Ga-RGD tumour accumulation was observed in all patients. Tumour SUVmax, measured at 60 minutes post injection, was 7.5±2.6 and correlated positively with tumour volume (R=0.69, P=0.041). Tracer accumulation in tumour tissue plateaued at 10 minutes after injection. Uptake in background tissue did not change over time.Conclusions: 68Ga-RGD PET/CT imaging of αvβ3 integrin expression in OSCC patients is feasible with adequate tumour-to-background ratios. It will provide more insight in angiogenesis as a hallmark of the head and neck squamous cell carcinomas’ tumour microenvironment

Imaging angiogenesis in patients with head and neck squamous cell carcinomas by [68Ga]Ga-DOTA-E-[c(RGDfK)]2 PET/CT

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Towards harmonized holmium-166 SPECT image quality for dosimetry: a multi-center, multi-vendor study

Background: Reliable dosimetry based on SPECT/CT imaging is essential to achieve personalized 166Ho-radioembolization treatment planning and evaluation. This study quantitatively evaluates multiple acquisition and reconstruction protocols for 166Ho-SPECT imaging based on data from five Dutch hospitals. We aim to recommend an imaging protocol which harmonizes 166Ho-SPECT images for reproducible and accurate dosimetry in a multi-scanner and multi-center setting. Methods: Cylindrical and NEMA IEC phantoms, filled with 166Ho-chloride, were imaged using seven SPECT/CT scanners from two vendors (GE HealthCare and Siemens Healthineers). Data were acquired with a photopeak window centered at 81 keV. Two adjacent scatter windows, and one upper scatter window at 118 keV were used for triple-energy window (TEW) and dual-energy window (DEW) scatter correction, respectively. The TEW and DEW reconstructions used vendor-specific software. Additionally, a vendor-neutral software package with Monte Carlo (MC) scatter correction (Hermes Medical Solutions) was used to study the influence of scanner hardware on the image quality. System sensitivity was measured in projection data of the cylindrical phantom. The axial uniformity in the cylindrical phantom was used to characterize the impact of the scatter correction method. The image quality was evaluated by the coefficient of variation (COV; noise), the contrast recovery coefficients (CRCs) and contrast-to-noise ratios (CNRs). Results: TEW scatter correction resulted in superior uniformity and higher CRCs compared to the DEW (CRC for the largest sphere over all scanners, mean ± SD (range): TEW 0.54 ± 0.07 (0.36–0.65), DEW 0.44 ± 0.04 (0.34–0.51)). DEW resulted in lower noise levels compared to TEW (16% lower on average). The DEW and TEW images resulted in comparable CNRs. The system sensitivities and the vendor-neutral image reconstructions demonstrated differences in hardware between the two vendors, most likely due to the characteristics of the vendor-specific medium energy collimator. Conclusion: This study demonstrates that TEW scatter correction increases the accuracy of 166Ho-SPECT images compared to DEW, and we henceforth recommend adopting this method in the clinical 166Ho-dosimetry workflow. Scanner hardware has a substantial impact on the characteristics of the acquired data, and identical reconstruction settings will therefore not automatically lead to harmonized image quality