Citation: Champendal, M.; Jreige, M.; Nicod Lalonde, M.; Pires Jorge, J.A.; Matter, M.; Sykiotis, G.P.; Prior, J.O. Feasibility and Performance of Free-Hand Single-Photon Computed Tomography/Ultrasonography for Preoperative Parathyroid Adenoma Localization: A Pilot Study. Diagnostics 2023, 13, 2200. https:// doi.org/10.3390/ diagnostics13132200 Academic Editor: Ayman El-Baz Received: 25 April 2023 Revised: 11 June 2023 Accepted: 19 June 2023 Published: 28 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). diagnostics Article Feasibility and Performance of Free-Hand Single-Photon Computed Tomography/Ultrasonography for Preoperative Parathyroid Adenoma Localization: A Pilot Study Mélanie Champendal 1 , Mario Jreige 2 , Marie Nicod Lalonde 2, * , José A. Pires Jorge 1 , Maurice Matter 3 , Gerasimos P. Sykiotis 4 and John O. Prior 2 1 School of Health Sciences HESAV, HES-SO, University of Applied Sciences Western Switzerland, 1011 Lausanne, Switzerland; melanie.champendal@hesav.ch (M.C.); jose.jorge@hesav.ch (J.A.P.J.) 2 Nuclear Medicine and Molecular Imaging Department, Lausanne University Hospital (CHUV), University of Lausanne, 1011 Lausanne, Switzerland; mario.jreige@chuv.ch (M.J.); john.prior@chuv.ch (J.O.P.) 3 Visceral Surgery Department, Lausanne University Hospital (CHUV), University of Lausanne, 1011 Lausanne, Switzerland; maurice.matter@chuv.ch 4 Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital (CHUV), University of Lausanne, 1011 Lausanne, Switzerland; gerasimos.sykiotis@chuv.ch * Correspondence: marie.nicod-lalonde@chuv.ch; Tel.: +41-795565561 Abstract: The aim of this prospective pilot study was to evaluate the feasibility of a new hybrid imag- ing modality, free-hand single-photon computed tomography/ultrasonography (fhSPECT/US), for preoperative localization of parathyroid adenomas and to compare its performance with conventional ultrasonography and SPECT/CT. Twelve patients diagnosed with primary hyperparathyroidism underwent sequentially US and parathyroid scintigraphy, including SPECT/CT, followed by fh- SPECT/US, allowing for real-time fusion between US and freehand-generated gamma-camera images. The fhSPECT/US detection rates were correlated with histopathology, when available, or with the imaging modality showing the most lesions. Based on a per patient analysis, the detection rate was significantly different when comparing SPECT/CT to fhSPECT/US (p = 0.03), and not significantly different when comparing SPECT/CT to US (p = 0.16) and US to fhSPECT/US (p = 0.08). Based on a per-lesion analysis, the detection rate of SPECT/CT was significantly higher than that of US (p = 0.01) and fhSEPCT/US (p = 0.003), and there was no significant difference in detection rate when comparing US to fhSPECT/US (p = 0.08). The main perceived limitations of fhSPECT/US in lesion detection were: (i) lesions localized at a depth ≥4.5 cm; (ii) imperfect image fusion due to tissue compression; (iii) limited spatial manipulation ability of the SPECT mobile camera handheld probe; and (iv) a wide spread of detected activity. In conclusion, clinical use of fhSPECT/US for localization of parathyroid adenomas is feasible, but shows lower sensitivity than conventional modalities and requires technical improvements. Keywords: hybrid imaging; SPECT/CT; US; handheld gamma camera; parathyroid adenoma; primary hyperparathyroidism 1. Introduction Primary hyperparathyroidism (pHPT) is a common endocrine disorder and the most frequent disorder of the parathyroid glands, affecting women above the age of 50 more often than men [1,2]. In approximately 80–90% of cases, the cause of pHPT is a solitary parathyroid adenoma. Parathyroid adenomas secrete increased amounts of parathyroid hormone (PTH), which causes hypercalcaemia and can lead to osteopenia, osteoporosis, nephrocalcinosis, or urinary tract lithiasis [3,4]. The main treatment for pHPT is surgery, usually a minimally invasive parathyroidec- tomy in the case of solitary adenomas. Preoperative imaging is indicated to localize Diagnostics 2023, 13, 2200. https://doi.org/10.3390/diagnostics13132200 https://www.mdpi.com/journal/diagnostics