NIRAF-Guided Parathyroid Identification During Thyroidectomy

Participants undergo standard thyroidectomy under white light using the same parathyroid-preservation principles, training standards, and postoperative endocrine management as the intervention group. The surgeon records the initial white-light gland assessment and intended action, followed by a brief white-light reassessment at the corresponding stage used for NIRAF assessment in the intervention group. Conventional autotransplantation is permitted when a devascularized or excised gland is identified by standard methods and rescue is clinically appropriate and oncologically safe. Experimental NIRAF imaging does not guide in vivo or specimen-related decisions in this group. Extra dissection solely to identify every gland is not required.

Participants undergo standard thyroidectomy with the same preservation principles and postoperative endocrine management as controls, plus modified Meta Quest NIRAF imaging. The surgeon first records glands identified under white light and the intended operative action. Brief in vivo NIRAF mapping is then performed after exposure, early enough to inform preservation before irreversible dissection, followed by ex vivo imaging of the removed specimen. Additional or corrected findings and resulting management changes are documented for independent CSE review. Rescue/autotransplantation is permitted when clinically appropriate and oncologically safe. Fluorescence alone does not establish tissue identity or vascular viability, and retained glands are not biopsied for research.

A modified Meta Quest head-mounted stereoscopic goggle system configured for label-free near-infrared autofluorescence imaging. The system delivers near-infrared excitation at approximately 780 nm and detects parathyroid autofluorescence centered near 800 nm. No injected dye or external contrast agent is administered. The device is used briefly after thyroid exposure for in vivo mapping and after thyroid resection for ex vivo specimen interrogation.

• Modified Meta Quest NIRAF goggles

Proportion of randomized Component B participants with serum intact PTH below the testing laboratory's assay-specific lower limit of normal, regardless of concurrent calcium or symptoms. The site records the assay, units, and reference interval before revised assessments begin and applies the same interpretation in both groups. No universal numeric cutoff or assay manufacturer is specified. The sample closest to 18 hours within the 12-to-24-hour window is used; ties use the earlier sample. Absence of a valid in-window sample is missing, not normal. Necessary calcium or active-vitamin-D treatment is not withheld for sampling; dose and timing are recorded. This is the sole randomized primary outcome.

Proportion of all randomized Component B participants with intact PTH below the same prespecified assay-specific lower limit of normal used for the primary endpoint, regardless of their initial postoperative PTH status. This is the key secondary outcome. Confirmatory testing at a two-sided 0.05 level follows a fixed sequence and occurs only if the primary comparison is statistically significant; estimates and confidence intervals are reported regardless.

Proportion of randomized Component B participants with histologically confirmed parathyroid tissue in material removed during the index operation. Clinically removed tissue is processed comparably in both groups, with pathology review masked to allocation where feasible. Counts of distinct glands and tissue fragments are reported separately, as are removal reasons, including deliberate, unavoidable, or inadvertent excision. No retained gland is biopsied for research.

Proportion of randomized Component B participants with albumin-adjusted total calcium below the prespecified laboratory lower limit of normal in the primary 12-to-24-hour postoperative blood sample. The laboratory reference range and calcium adjustment method are fixed before implementation and used identically in both groups. Symptoms and calcium/active-vitamin-D treatment at sampling are recorded separately.

Proportions of randomized Component B participants classified at each assessment as documented normal function/recovery, ongoing dysfunction, or indeterminate by endocrine review masked to allocation. Normal function/recovery requires intact PTH and albumin-adjusted calcium within their reference ranges after at least 14 consecutive days without active vitamin D or therapeutic calcium. This is an operational study assessment rule; withdrawal is considered only when clinically safe under endocrine supervision. Continued prescribing alone does not establish dysfunction. Recovery is also summarized among participants with earlier postoperative dysfunction. Six-month dysfunction is not labeled permanent hypoparathyroidism.

Number of postoperative days on which each randomized Component B participant actually takes therapeutic active vitamin D, such as calcitriol or alfacalcidol, for postoperative parathyroid dysfunction. Agent, dose, indication, and reported adherence are recorded. Prophylactic use is distinguished from therapeutic use; nutritional vitamin D is excluded. Confirmed absence of therapeutic use contributes zero days. Treatment initiation and taper follow the same clinical algorithm in both groups.

Proportion of randomized Component B participants with new symptoms or signs attributed to hypocalcemia and contemporaneous biochemical confirmation of low calcium under prespecified clinical criteria. Episodes lacking biochemical confirmation are recorded separately. Events are ascertained from clinical records and patient confirmation; collection may be completed at the six-week visit without changing the 30-day event window.

Number of postoperative days on which each randomized Component B participant actually takes therapeutic oral calcium for postoperative parathyroid dysfunction. Elemental-calcium dose, indication, and reported adherence are recorded. Prophylactic use is distinguished from therapeutic use; dietary calcium is excluded. Confirmed absence of therapeutic use contributes zero days. Treatment initiation and taper follow the same clinical algorithm in both groups.

Proportion of randomized Component B participants with at least one emergency-department attendance attributed to hypocalcemia. Event dates, indications, and number of attendances are recorded from clinical records and patient confirmation. Hospital readmissions are reported as a separate outcome. Ascertainment may be completed at the six-week visit without changing the 30-day event window.

Duration of the index thyroid operation in minutes, measured from initial incision to completion of skin closure, for each randomized Component B participant. NIRAF mapping time is recorded separately.

Proportion of randomized Component B participants undergoing clinically indicated parathyroid autotransplantation during the index operation. Reason, detection method, tissue source, implant site, number of distinct glands when determinable, and number of fragments implanted are recorded separately. Conventional and NIRAF-prompted rescue are distinguished. Autotransplantation alone does not establish later graft function.

Proportion of randomized Component B participants with at least one unplanned hospital readmission attributed to hypocalcemia. Dates, indications, and numbers of admissions are recorded using clinical records and patient confirmation. Emergency-department attendance without admission is recorded separately. Ascertainment may be completed at the six-week visit without changing the 30-day event window.

Proportion of randomized Component B participants receiving intravenous calcium for postoperative hypocalcemia. Treatment indication, dates, doses, and care setting are recorded. Both groups follow the same clinical treatment algorithm.

Proportion of randomized Component B participants with postoperative bleeding or neck hematoma requiring a clinical intervention, including operative evacuation or another documented therapeutic procedure. Event date, severity, and intervention are recorded; subsequent resolution is followed clinically.

Proportion of randomized Component B participants with new postoperative vocal-fold dysfunction confirmed by laryngoscopy, interpreted relative to preoperative vocal-fold status. Laterality, date of detection, and subsequent recovery are documented. Cases lacking adequate baseline or confirmatory assessment are identified separately.

Proportion of intervention-group participants with a device failure or interruption that prevents or disrupts the planned NIRAF assessment. Type, duration, reason, mitigation, and whether the operation continues without device guidance are documented. Failures and interruptions are also reported separately, and affected participants remain in the randomized intention-to-treat analysis.

Proportion of intervention-group participants with at least one adverse event assessed as related to the investigational NIRAF imaging system. Event type, onset, severity, seriousness, relatedness, action taken, and outcome are recorded. All other surgical adverse events are collected under the common safety procedures in both groups.

Proportion of randomized Component B participants with albumin-adjusted total calcium below the prespecified laboratory lower limit of normal at each scheduled follow-up assessment, reported separately by time point. The calcium adjustment method is fixed and applied identically in both groups. Treatment at sampling and intervening clinically documented hypocalcemic episodes are recorded.

Proportion of intervention-group participants with at least one independently adjudicated clinically significant event (CSE): new or corrected NIRAF information producing a documented clinically meaningful change in operative management. Categories include altered dissection to preserve an additional gland, corrected tissue identification that changes management, and clinically indicated rescue/autotransplantation after specimen detection. Additional fluorescence or confidence without a management change is not a CSE. Review uses pre-imaging findings and intended actions, subsequent findings, changed actions, final disposition, and supporting records without postoperative endocrine outcomes where feasible. Consecutive intervention cases, including failures and no-change cases, are accounted for; missing documentation is reported. Event counts by category are summarized. This is a key device-performance endpoint, supportive to the randomized clinical primary endpoint.

Number of distinct clinically adjudicated parathyroid glands identified per intervention-group participant during white-light and NIRAF assessment, with the identification method recorded. Fluorescent sites not adjudicated as parathyroid are reported separately. Participants with no additional finding and device failures remain documented. Gland counts are summarized at participant level; tissue fragments are not counted as separate glands.

Proportion of intervention-group participants with at least one additional clinically adjudicated parathyroid gland identified with NIRAF beyond the surgeon's recorded initial white-light declaration. This is the principal endpoint of the nested device-performance assessment, not an additional randomized primary endpoint. Consecutive assigned intervention cases, including no additional findings and device failures, are accounted for. In situ identity is clinically adjudicated; pathology is used only for tissue removed for clinical reasons. Missing documentation is reported separately. Additional identification alone does not establish a CSE or preserved endocrine function.

Elapsed time from the start of NIRAF assessment to the first clinically adjudicated parathyroid identification, and total NIRAF mapping duration, reported separately in seconds for intervention-group participants. Cases with no gland identified are reported explicitly rather than assigned a zero identification time. Device interruptions and failed assessments are recorded.

Descriptive proportion of ex vivo NIRAF-positive, suture-marked foci from Component A that routine or targeted pathology confirms as parathyroid tissue. Denominator: marked foci with an interpretable pathology result; numerator: confirmed parathyroid foci. Participant-level counts and uninterpretable or missing results are also summarized. This exploratory registry measure is added after study initiation; reporting identifies the applicable protocol and observation dates. It does not estimate sensitivity or specificity and does not validate the identity of every gland preserved in situ.

Number of distinct additional clinically adjudicated parathyroid glands identified with NIRAF beyond the surgeon's recorded initial white-light declaration, per intervention-group participant. A documented absence of additional glands contributes zero. Uncertain identity, tissue fragments, and missing documentation are distinguished. Participant-level distributions are reported; glands are not treated as independent participants.