Zaid Al-Difaie

Purpose: Dual-energy computed tomography (DECT) allows for the measurement of iodine concentration, a component for the synthesis of thyroid hormones. DECT can create virtual non-contrast (VNC) images, potentially reducing radiation exposure. This study explores the correlations between thyroid function and iodine concentration, as well as the relationship between thyroid densities in true non-contrast (TNC) and virtual non-contrast (VNC) images and thyroid function. Methods: The study involved 87 patients undergoing 4D-CT imaging with single and dual-energy scans for diagnosing primary hyperparathyroidism. Thyroid densities and iodine concentrations were measured across all scanning phases. These measurements were correlated with thyroid function, indicated by TSH and FT4 levels. Differences in thyroid density between post-contrast phases and TNC phases (ΔHU) were analyzed for correlations with thyroid function and iodine concentrations. Results: Positive correlations between iodine concentrations and TSH were found, with Spearman’s coefficients (R) of 0.414, 0.361, and 0.349 for non-contrast, arterial, and venous phases, respectively. Thyroid density on TNC showed significant positive correlations with TSH levels (R = 0.436), consistently across both single- (R = 0.435) and dual-energy (R = 0.422) scans. Thyroid densities on VNC images did not correlate with TSH or FT4. Differences in density between contrast and non-contrast scans (ΔHU) negatively correlated with TSH (p = 0.002). Conclusions: DECT-derived iodine concentrations and thyroid densities in non-contrast CT scans demonstrated positive correlations with thyroid function, in contrast to thyroid densities on VNC scans. This indicates that VNC images are unsuitable for this purpose. Correlations between ΔHU and TSH suggest a potential link between the thyroid’s structural properties to capture iodine and its hormonal function. This study underscores the potential value of (DE-) CT imaging for evaluating thyroid function as an additional benefit in head and neck scans.

The differentiation between malignant and benign thyroid nodules represents a significant challenge for clinicians globally. The identification of volatile organic compounds (VOCs) has emerged as a novel approach in the field of cancer diagnosis. This prospective pilot study aims to identify VOCs in exhaled breath, blood, and urine that can differentiate benign from malignant thyroid nodules using gas chromatography-ion mobility spectrometry (GC-IMS). Patients with thyroid nodules scheduled for surgery were enrolled at the Maastricht University Medical Center (MUMC+). Breath samples were analyzed using a BreathSpec GC-IMS machine (G.A.S. Dortmund, Germany), specifically designed for breath analysis. All blood and urine samples were analyzed using a separate GC-IMS device, the FlavourSpec® (G.A.S., Dortmund, Germany). In this proof-of-concept study, 70 consecutive patients undergoing thyroid surgery at MUMC+ were included. Of these patients, 29 were confirmed to have thyroid cancer after surgical resection. The overall analysis did not reveal statistically significant differences in VOCs in breath, urine and blood, between patients with benign and malignant thyroid cancer. This proof-of-concept study demonstrated that GC-IMS could not effectively differentiate between the VOC profiles of malignant and benign thyroid nodules. However, due to the small sample size of this study, larger prospective studies are needed to investigate the potential of using VOCs to distinguish between benign and malignant thyroid nodules. Additionally, future research should focus on identifying potential confounding factors that may influence patient VOC profiles. (NCT04883294).

Accurate preoperative localization is crucial for successful minimally invasive parathyroidectomy in primary hyperparathyroidism (PHPT). Preoperative localization can be challenging in patients with recurrent and/or multigland disease (MGD). This has led clinicians to investigate multiple imaging techniques, most of which are associated with radiation exposure. Magnetic resonance imaging (MRI) offers ionizing radiation-free and accurate imaging, making it an attractive alternative imaging modality. The objective of this systematic review is to provide an overview of the diagnostic performance of MRI in the localization of PHPT. PubMed and Embase libraries were searched from 1 January 2000 to 31 March 2023. Studies were included that investigated MRI techniques for the localization of PHPT. The exclusion criteria were (1) secondary/tertiary hyperparathyroidism, (2) studies that provided no diagnostic performance values, (3) studies published before 2000, and (4) studies using 0.5 Tesla MRI scanners. Twenty-four articles were included in the systematic review, with a total of 1127 patients with PHPT. In 14 studies investigating conventional MRI for PHPT localization, sensitivities varied between 39.1% and 94.3%. When employing more advanced MRI protocols like 4D MRI for PHPT localization in 11 studies, sensitivities ranged from 55.6% to 100%. The combination of MR imaging with functional techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy, with sensitivities ranging from 84.2% to 100% in five studies. Despite the limitations of the available evidence, the results of this review indicate that the combination of MR imaging with functional imaging techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy. Further research on emerging MR imaging modalities, such as 4D MRI and PET/MRI, is warranted, as MRI exposes patients to minimal or no ionizing radiation compared to other imaging modalities.

Low baseline levels of parathyroid hormone (PTH) are associated with a higher rate of multiglandular disease, lower localization rates of preoperative imaging modalities, and a higher rate of unsuccessful minimally invasive parathyroidectomies. The objective of this study is to assess the diagnostic value of four-dimensional dynamic computed tomography (4D-CT) in localizing primary hyperparathyroidism (pHPT) in patients with low baseline PTH levels, compared to patients with high baseline PTH levels. Patients with pHPT who received a 4D-CT scan as part of their standard diagnostic evaluation were divided into two groups based on the following criteria: (1) preoperative PTH levels less than 100 pg/mL and (2) patients with preoperative PTH levels greater than 100 pg/mL. All patients underwent parathyroidectomy based on 4D-CT findings, with intraoperative parathyroid hormone monitoring. The lesion-based sensitivity of 4D-CT was 88% in patients with low baseline PTH levels and 94.7% in patients with high baseline PTH levels (p = 0.33). However, the success rate of image-guided resection based on 4D-CT findings was 71.4% in the low baseline PTH group compared to 90.6% in the high baseline PTH group (p = 0.06). Our study demonstrated that 4D-CT has a high lesion-based sensitivity in patients with pHPT and low baseline PTH levels but led to a relatively low rate of successful image-guided resection in patients with low baseline PTH levels. Therefore, it is important to exercise increased caution during 4D-CT-guided surgical exploration of patients with low baseline PTH levels to ensure successful surgical resection of all parathyroid lesions.

Background: Dual-energy computed tomography (DECT) is an advanced imaging method that enables reconstruction of virtual non-contrast (VNC) images from a contrast-enhanced acquisition. This has the potential to reduce radiation exposure by eliminating the need for a true non-contrast (TNC) phase. Purpose: The purpose is to evaluate the feasibility of VNC images in the neck region. Materials and methods: A total of 100 patients underwent a DECT scan as part of diagnostic workup of primary hyperparathyroidism. VNC images were reconstructed from 30 s (arterial) and 50 s (venous) post-contrast scans. Regions of interest (ROIs) were placed in thyroid tissue, lymph node, carotid artery, jugular vein, fat, and sternocleidomastoid muscle. Mean densities of all anatomical structures were compared between VNC and TNC images. Results: For all anatomical structures except the thyroid gland, the difference in mean density between TNC and VNC images was less than 15 HU. The mean difference in density between TNC and VNC images of the thyroid was 53.2 HU (95% CI 46.8; 59.6, p = <0.001). Conclusion: This study demonstrated an acceptable agreement in density between true non-contrast and virtual non-contrast images for most anatomical structures in the neck region. Therefore, VNC images may have the potential to replace TNC images in the neck. However, due to significant differences in CT density of thyroid tissue, true non-contrast imaging cannot be directly substituted by virtual non-contrast imaging when examining the thyroid and its surrounding tissue.

Near-infrared fluorescence (NIRF) image-guided surgery is a useful tool that can help reduce perioperative complications and improve tissue recognition. Indocyanine green (ICG) dye is the most frequently used in clinical studies. ICG NIRF imaging has been used for lymph node identification. However, there are still many challenges in lymph node identification by ICG. There is increasing evidence that methylene blue (MB), another clinically applicable fluorescent dye, can also be useful in the intraoperative fluorescence-guided identification of structures and tissues. We hypothesized that MB NIRF imaging could be used for lymph node identification. The aim of this study was to evaluate the feasibility of intraoperative lymph node fluorescence detection using intravenously (IV) administered MB and compare it to ICG via a camera that has two dedicated near-infrared (NIR) channels. Three pigs were used in this study. ICG (0.2 mg/kg) was administered via a peripheral venous catheter followed by immediate administration of MB (0.25 mg/kg). NIRF images were acquired as video recordings at different time points (every 10 min) over an hour using the QUEST SPECTRUM^® 3 system (Quest Medical Imaging, Middenmeer, The Netherlands), which has two dedicated NIR channels for simultaneous intraoperative fluorescence guidance. The 800 nm channel was used to capture ICG fluorescence and the 700 nm channel was used for MB. The target (lymph nodes and small bowel) and the background (vessels-free field of the mesentery) were highlighted as the regions of interest (ROIs), and corresponding fluorescence intensities (FI) from these ROIs were measured. The target-to-background ratio (TBR) was then computed as the mean FI of the target minus the mean FI of the background divided by the mean FI of the background. In all included animals, a clear identification of lymph nodes was achieved at all time points. The mean TBR of ICG in lymph nodes and small bowel was 4.57 ± 1.00 and 4.37 ± 1.70, respectively for the overall experimental time. Regarding MB, the mean TBR in lymph nodes and small bowel was 4.60 ± 0.92 and 3.27 ± 0.62, respectively. The Mann-Whitney U test of the lymph node TBR/small bowel TBR showed that the TBR ratio of MB was statistically significantly higher than ICG. The fluorescence optical imaging technology used allows for double-wavelength assessment. This feasibility study proves that lymph nodes can be discriminated using two different fluorophores (MB and ICG) with different wavelengths. The results suggest that MB has a promising potential to be used to detect lymphatic tissue during image-guided surgery. Further preclinical trials are needed before clinical translation.

This proof-of-principle study investigates the diagnostic performance of the Aeonose in differentiating malignant from benign thyroid diseases based on volatile organic compound analysis in exhaled breath. All patients with a suspicious thyroid nodule planned for surgery, exhaled in the Aeonose. Definitive diagnosis was provided by histopathological determination after surgical resection. Breath samples were analyzed utilizing artificial neural networking. About 133 participants were included, 48 of whom were diagnosed with well-differentiated thyroid cancer. A sensitivity of 0.73 and a negative predictive value (NPV) of 0.82 were found. The sensitivity and NPV improved to 0.94 and 0.95 respectively after adding clinical variables via multivariate logistic regression analysis. This study demonstrates the feasibility of the Aeonose to discriminate between malignant and benign thyroid disease. With a high NPV, low cost, and non-invasive nature, the Aeonose may be a promising diagnostic tool in the detection of thyroid cancer.