The imaging tree of parathyroid diseases - Improving surgical outcomes by illuminating parathyroid glands

The current thesis investigates diagnostic molecular, optical and optoacoustic imaging techniques in parathyroid diseases. These imaging modalities may support surgical planning and have the potential to provide critical anatomical and biological information before and during surgery. In the first part of this thesis, we found that employing nuclear imaging techniques according to a standardized method in patients with primary hyperparathyroidism allows for the localization of parathyroid diseases with high accuracy before surgery. As a result, a minimally invasive surgical intervention is sufficient in these patients with fewer complications.The second part of this thesis focuses on preserving parathyroid glands during thyroid surgery to prevent hypoparathyroidism using optical fluorescence and optoacoustic imaging. Optical fluorescence imaging, where a fluorescent imaging agent lights up blood vessels during surgery, can assist in this clinical challenge. Moreover, optoacoustic imaging, an imaging modality that uses light to generate ultrasound waves, thereby providing both anatomical and biological information about the tissue, may be of help. We show the potential of standardized and quantitative optical and optoacoustic imaging in thyroid surgery patients to support clinical decision-making and ultimately prevent parathyroid function impairment. To incorporate these imaging techniques into the standard of care, we need to collaborate internationally to standardize evidence-based imaging and treatment guidelines. Eventually, illuminating parathyroid glands using these different techniques on the imaging tree of parathyroid diseases may guide surgical decision-making and improve surgical outcomes

The imaging tree of parathyroid diseases - Improving surgical outcomes by illuminating parathyroid glands

The current thesis investigates diagnostic molecular, optical and optoacoustic imaging techniques in parathyroid diseases. These imaging modalities may support surgical planning and have the potential to provide critical anatomical and biological information before and during surgery. In the first part of this thesis, we found that employing nuclear imaging techniques according to a standardized method in patients with primary hyperparathyroidism allows for the localization of parathyroid diseases with high accuracy before surgery. As a result, a minimally invasive surgical intervention is sufficient in these patients with fewer complications. The second part of this thesis focuses on preserving parathyroid glands during thyroid surgery to prevent hypoparathyroidism using optical fluorescence and optoacoustic imaging. Optical fluorescence imaging, where a fluorescent imaging agent lights up blood vessels during surgery, can assist in this clinical challenge. Moreover, optoacoustic imaging, an imaging modality that uses light to generate ultrasound waves, thereby providing both anatomical and biological information about the tissue, may be of help. We show the potential of standardized and quantitative optical and optoacoustic imaging in thyroid surgery patients to support clinical decision-making and ultimately prevent parathyroid function impairment. To incorporate these imaging techniques into the standard of care, we need to collaborate internationally to standardize evidence-based imaging and treatment guidelines. Eventually, illuminating parathyroid glands using these different techniques on the imaging tree of parathyroid diseases may guide surgical decision-making and improve surgical outcomes

Heterogeneity in Utilization of Optical Imaging Guided Surgery for Identifying or Preserving the Parathyroid Glands-A Meta-Narrative Review

Background: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy. Over the past years, optical imaging techniques, such as parathyroid autofluorescence, indocyanine green (ICG) angiography, and laser speckle contrast imaging (LSCI) have been employed to save parathyroid glands during thyroid surgery. This study provides an overview of the utilized methods of the optical imaging techniques during total thyroidectomy for parathyroid gland identification and preservation. Methods: PUBMED, EMBASE and Web of Science were searched for studies written in the English language utilizing parathyroid autofluorescence, ICG-angiography, or LSCI during total thyroidectomy to support parathyroid gland identification or preservation. Case reports, reviews, meta-analyses, animal studies, and post-mortem studies were excluded after the title and abstract screening. The data of the studies were analyzed qualitatively, with a focus on the methodologies employed. Results: In total, 59 articles were included with a total of 6190 patients. Overall, 38 studies reported using parathyroid autofluorescence, 24 using ICG-angiography, and 2 using LSCI. The heterogeneity between the utilized methodology in the studies was large, and in particular, regarding study protocols, imaging techniques, and the standardization of the imaging protocol. Conclusion: The diverse application of optical imaging techniques and a lack of standardization and quantification leads to heterogeneous conclusions regarding their clinical value. Worldwide consensus on imaging protocols is needed to establish the clinical utility of these techniques for parathyroid gland identification and preservation

Non-adherence to consensus guidelines on preoperative imaging in surgery for primary hyperparathyroidism

Objective: The aim of this study was to determine the adherence to consensus guidelines on preoperative imaging of patients with primary hyperparathyroidism (pHPT) in real local practice. Methods: This was a retrospective multicenter cohort study of 411 patients undergoing parathyroidectomy for pHPT from 2007 to 2017 in three referral centers. Results: In 286/411 patients (69%) the preoperative imaging workup adhered to guidelines (utilizing ultrasound and parathyroid scintigraphy). In patients in whom guidelines were followed 63% were discharged within one day versus 37% in whom guidelines were not followed (P< .0005). The use of a bimodality imaging workup, starting with ultrasound and parathyroid scintigraphy followed by imaging upscaling aiming for anatomical and functional concordance, was a predictor for the performance of a minimally invasive parathyroidectomy (OR 4.098, 95% CI 2.296-7.315,P< .0005). Conclusion: The level of compliance to preoperative imaging guidelines is suboptimal in this population. Patients in whom adherence was achieved showed a shorter length of stay. More education of physicians is required regarding the appropriate preoperative imaging workup in pHPT

Localization of parathyroid adenomas using 11C-methionine pet after prior inconclusive imaging

Purpose: Minimally invasive parathyroidectomy (MIP) is the recommended treatment in primary hyperparathyroidism (pHPT) for which accurate preoperative localization is essential. The current imaging standard consists of cervical ultrasonography (cUS) and MIBI-SPECT/CT. 11C-MET PET/CT has a higher resolution than MIBI-SPECT/CT. The aim of this study was to determine the diagnostic performance of 11CMET PET/CT after initial inconclusive or negative localization.  Methods: We performed a retrospective single center cohort study of patients with pHPT undergoing parathyroid surgery after prior negative imaging and later localization by means of 11C-MET PET/CT between 2006 and 2014. Preoperative localization by 11C-MET PET/CT was compared with later surgical localization, intraoperative quick PTH (IOPTH), duration of surgery, histopathology, and follow-up data. Also, differences in duration of surgery between the groups with and without correct preoperative localization were analyzed.  Results: In 18/28 included patients a positive 11C-MET-PET/CT result corresponded to the surgical localized adenoma (64%). In 3/28 patients imaging was false positive and no adenoma was found. In 7/28 patients imaging was false negative at the side of the surgically identified adenoma. Sensitivity of 11C-MET PET/ CT was 72% (18/25). Duration of surgery of correctly localized patients was significantly shorter compared to falsely negative localized patients (p = 0.045).  Conclusion: In an intention to treat 11C-MET-PET/CT correctly localized the parathyroid adenoma in 18/28 (64%) patients, after previous negative imaging. A preoperatively correct localized adenoma leads to a more focused surgical approach (MIP) potentially reducing duration of surgery and potentially healthcare costs

The satisfaction regarding handovers between ambulance and emergency department nurses:an observational study

Background: A thorough handover in the emergency department (ED) is of great importance for improving the quality and safety in the chain of care. The satisfaction of handover may reflect the quality of handover. Research to discover the variables influencing the satisfaction of handovers is scarce. The goal of this study was to determine the factors influencing the satisfaction regarding handovers from ambulance and ED nurses. Methods: We performed a prospective observational study in the University Medical Center of Groningen. Data regarding prehospital-hospital handovers has been collected by observing handovers and assessing patient chart information. Data regarding the satisfaction has been collected with a questionnaire including a 5-point scale for the level of satisfaction. Results: In total, 97 handovers were observed and 97 ambulance nurses and 89 ED nurses completed the questionnaire. The satisfaction of ambulance nurses showed a negative correlation with the waiting time prior to handover (r=-.287, p=.004) and a positive correlation with the presence of a physician in the receiving team (r=.224, p=.028). The satisfaction of ED nurses showed a positive correlation with the use of the ABCDE (r=.288, p=.006) and AMPLE instrument (r=.208, p=.050). Conclusion: The satisfaction of ambulance and ED nurses as sender or receiver of the handover is determined by different factors. The satisfaction of ambulance nurses is mainly affected by the waiting time and presence of a physician, while the satisfaction of ED nurses is affected by the use of handover instruments and the completeness of medical information

Quality Indicators for the Diagnosis and Management of Primary Hyperparathyroidism

IMPORTANCE Primary hyperparathyroidism (pHPT) is a common endocrine disorder with many diagnostic and treatment challenges. Despite high-quality guidelines, care is variable, and there is low adherence to evidence-based treatment pathways. OBJECTIVE To develop quality indicators (QIs) to evaluate the diagnosis and treatment of pHPT that could measure, improve, and optimize quality of care and outcomes for patients with this disease. DESIGN, SETTING, AND PARTICIPANTS This quality improvement study used a guideline-based approach to develop QIs that were ranked by a Canadian 9-member expert panel of 3 endocrinologists, 3 otolaryngologists, and 3 endocrine surgeons. Data were analyzed between September 2020 and May 2021. MAIN OUTCOMES AND MEASURES Candidate indicators (CIs) were extracted from published primary hyperparathyroidism guidelines and summarized with supporting evidence. The 9-member expert panel rated each CI on the validity, reliability, and feasibility of measurement. Final QIs were selected from CIs using the modified RAND-University of California, Los Angeles appropriateness methodology. All panelists were then asked to rank the top 5 QIs for primary, endocrine, and surgical care. RESULTS Forty QIs were identified and evaluated by the expert panel. After 2 rounds of evaluations and discussion, a total of 18 QIs were selected as appropriate measures of high-quality care. The top 5 QIs for primary, endocrine, and surgical care were selected following panelist rankings. CONCLUSIONS AND RELEVANCE This quality improvement study proposes 18 QIs for the diagnosis and management of pHPT. Furthermore, the top 5 QIs applicable to physicians commonly treating pHPT, including general physicians, internists, endocrinologists, otolaryngologists, and surgeons, are included. These QIs not only assess the quality of care to guide the process of improvement, but also can assess the implementation of evidence-based guideline recommendations. Using these indicators in clinical practice and health system registries can improve quality and cost-effectiveness of care for patients with pHPT

A Novel and Generic Workflow of Indocyanine Green Perfusion Assessment Integrating Standardization and Quantification Towards Clinical Implementation

OBJECTIVE: This study aims to generate a reproducible and generalizable Workflow model of ICG-angiography integrating Standardization and Quantification (WISQ) that can be applied uniformly within the surgical innovation realm independent of the user. SUMMARY BACKGROUND DATA: Tissue perfusion based on indocyanine green (ICG)-angiography is a rapidly growing application in surgical innovation. Interpretation of have been subjective and error-prone due to the lack of a standardized and quantitative ICG-workflow and analytical methodology. There is a clinical need for a more generic, reproducible, and quantitative ICG perfusion model for objective assessment of tissue perfusion. METHODS: In this multicenter, proof-of-concept study, we present a generic and reproducible ICG-workflow integrating standardization and quantification for perfusion assessment. To evaluate our model's clinical feasibility and reproducibility, we assessed the viability of parathyroid glands after performing thyroidectomy. Biochemical hypoparathyroidism was used as the postoperative endpoint and its correlation with ICG quantification intraoperatively. Parathyroid gland are an ideal model as parathyroid function post-surgery is only affected by perfusion. RESULTS: We show that visual -subjective- interpretation of ICG-angiography by experienced surgeons on parathyroid perfusion cannot reliably predict organ function impairment postoperatively, emphasizing the importance of an ICG quantification model. WISQ was able to standardize and quantify ICG-angiography and provided a robust and reproducible perfusion curve analysis. A low ingress slope of the perfusion curve combined with a compromised egress slope was indicative for parathyroid organ dysfunction in 100% of the cases. CONCLUSION: WISQ needs prospective validation in larger series and may eventually support clinical decision-making to predict and prevent postoperative organ function impairment in a large and varied surgical population

Towards in vivo characterization of thyroid nodules suspicious for malignancy using multispectral optoacoustic tomography

Purpose: Patient-tailored management of thyroid nodules requires improved risk of malignancy stratification by accurate preoperative nodule assessment, aiming to personalize decisions concerning diagnostics and treatment. Here, we perform an exploratory pilot study to identify possible patterns on multispectral optoacoustic tomography (MSOT) for thyroid malignancy stratification. For the first time, we directly correlate MSOT images with histopathology data on a detailed level. Methods: We use recently enhanced data processing and image reconstruction methods for MSOT to provide next-level image quality by means of improved spatial resolution and spectral contrast. We examine optoacoustic features in thyroid nodules associated with vascular patterns and correlate these directly with reference histopathology. Results: Our methods show the ability to resolve blood vessels with diameters of 250 μm at depths of up to 2 cm. The vessel diameters derived on MSOT showed an excellent correlation (R2-score of 0.9426) with the vessel diameters on histopathology. Subsequently, we identify features of malignancy observable in MSOT, such as intranodular microvascularity and extrathyroidal extension verified by histopathology. Despite these promising features in selected patients, we could not determine statistically relevant differences between benign and malignant thyroid nodules based on mean oxygen saturation in thyroid nodules. Thus, we illustrate general imaging artifacts of the whole field of optoacoustic imaging that reduce image fidelity and distort spectral contrast, which impedes quantification of chromophore presence based on mean concentrations. Conclusion: We recommend examining optoacoustic features in addition to chromophore quantification to rank malignancy risk. We present optoacoustic images of thyroid nodules with the highest spatial resolution and spectral contrast to date, directly correlated to histopathology, pushing the clinical translation of MSOT.</p