18F-fluorodeoxyglucose positron emission tomography/computed tomography as an adjunctive tool in the diagnosis of brain death/death by neurologic criteria (BD/DNC) with abnormal spinal reflexes: a series of case descriptions

Introduction

Brain death/death by neurologic criteria (BD/DNC) is defined as the complete and irreversible cessation of all brain functions, including those of the brainstem, respiratory, and autonomic systems. The first formal criteria for diagnosing BD/DNC were established by the Harvard Medical School in 1968 (1). China introduced its adult and pediatric BD/DNC determination criteria and operational guidelines in 2013 and 2019, respectively (2,3). Although the Pediatric and Adult BD/DNC Consensus Guideline was published in 2023, it emphasizes the need for further research to develop ancillary testing methods (4).

China’s clinical criteria for BD/DNC, while consistent with international standards, require confirmatory tests after clinical judgment. Despite the widespread application of short-latency somatosensory evoked potential (SLSEP) and transcranial Doppler (TCD) (2), no single method has demonstrated complete efficacy (5). SLSEP has limitations in diagnosing BD/DNC owing to its potential for false positives or negatives, variability in results based on technique, and limited sensitivity in severe brain damage, necessitating additional diagnostic tools for more accurate assessment (6). TCD is constrained by its susceptibility to false positives and negatives, as well as reduced sensitivity in detecting cerebral circulatory arrest under specific conditions, including hypothermia, low cardiac output, or skull abnormalities (7,8).

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) using 18F-fluorodeoxyglucose as a tracer is frequently employed in the clinical evaluation of tumors, inflammation, and infectious diseases. FDG-PET/computed tomography (CT), which integrates FDG-PET and CT, assesses the brain’s basal metabolic rate, facilitating the evaluation of metabolic changes across various brain regions. In BD/DNC, glucose metabolism is generally absent in the cortical regions responsible for consciousness, whereas minimal activity may still be observed in the brainstem, which governs basic life functions. The lack of glucose metabolism in specific regions, including cortical areas, correlates strongly with loss of consciousness, making FDG-PET/CT a useful tool in assessing BD/DNC (9).

Despite its potential, FDG-PET/CT remains underrepresented in current standards, consensus statements, and guidelines (4,10) and is infrequently applied in clinical practice (11). In this study, we conducted FDG-PET/CT imaging in four patients with severe brain injuries, including those with BD/DNC and with or without abnormal motor responses, to explore its applicability as an ancillary diagnostic tool for BD/DNC.

Methods

All procedures performed in this study were in accordance with the Helsinki Declaration and its subsequent amendments. This study was approved by the Ethics Review Board of Taizhou Hospital of Zhejiang Province, Affiliated with Wenzhou Medical University (Approval No. K20190602). Written informed consent was obtained from the patients or their next of kin for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

This case report retrospectively collected four cases to illustrate the value of FDG-PET/CT in diagnosing BD/DNC complicated by confounding factors. These included one patient with hypoxic-ischemic encephalopathy, one brain-dead patient without spinal reflexes, and two brain-dead patients with preserved spinal reflexes. All four patients were from the Department of Critical Care Medicine at the Taizhou Hospital of Zhejiang Province, affiliated with Wenzhou Medical University, an academic hospital. In addition to BD/DNC assessment (including brainstem reflex evaluation and spontaneous respiratory provocation test) and confirmatory tests [bedside electroencephalogram (EEG) monitoring and TCD detection], FDG-PET/CT imaging was performed.

Examination methods

Spontaneous respiratory provocation test

Prerequisites were as follows: core body temperature ≥36.5 °C, systolic blood pressure ≥90 mmHg, arterial partial pressure of oxygen (PaO₂) ≥200 mmHg, and since none of the four patients had a history of chronic CO₂ retention, arterial partial pressure of carbon dioxide (PaCO₂) was adjusted to the normal range (35–45 mmHg).

Test procedure: arterial blood was drawn to measure baseline PaCO₂. The patient was weaned off the ventilator. An oxygen delivery catheter was inserted at the carina level through an artificial airway and infused with 100% oxygen at a rate of 6 L/min. The chest and abdomen were closely observed for respiratory movement. After 8–10 min off the ventilator, arterial blood was drawn again to measure PaCO₂. Restore mechanical ventilation.

Result interpretation: if the patient meets all of the following three criteria—(I) no spontaneous respiration or respiratory effort; (II) arterial pH <7.30; (III) PaCO2 ≥60 mmHg and at least 20 mmHg higher than the patient’s baseline PaCO2 prior to the apnea test, spontaneous respiration can be ruled out.

Bedside EEG monitoring

The EEG was performed using the Natus EEG measurement system (USA). The parameter settings included impedances ranging from >100 Ω to <5 kΩ between the electrode and the scalp. The impedances of the corresponding electrodes on both sides were matched. High-frequency filter, 30–75 Hz; low-frequency filter, 0.5 Hz. Sensitivity: 2 µV/mm. Notch filter: 50 Hz.

Electrode placement: a minimum of eight recording electrodes were placed according to the International 10–20 system. The electrodes were positioned at the following sites: Frontal pole (Fp1 and Fp2), central (C3 and C4), occipital (O1 and O2), and middle temporal (T3 and T4) regions. Reference electrodes were placed on the bilateral mastoids. A ground electrode was positioned at the midpoint of the frontal pole (FPz), and a common reference electrode was placed at the central midline point (Cz).

Result interpretation: grade I—predominantly theta rhythm with occasional alpha and delta waves; grade II—predominantly delta rhythm with occasional theta waves; grade III—diffuse delta waves interspersed with periods of flat EEG, also known as the burst suppression pattern; grade IV—predominantly flat EEG with intermittent delta waves. An EEG exhibiting a sustained electrical resting state (wave activity ≤2 µV) for ≥30 min is consistent with BD/DNC.

TCD detection

TCD ultrasound was performed using a 1.6 or 2.0 MHz pulsed wave Doppler ultrasound probe. The output power was adjusted accordingly. The sampling volume was set between 10 and 15 mm. The screen scan speed was set at 6–8 s/screen. The Doppler frequency filter was set to a low filter status (≤50 Hz).

Examination sites and vessels: the temporal window—bilateral middle cerebral arteries (MCA), and terminal internal carotid arteries were examined; occipital window—vertebral arteries and basilar artery (BA) were assessed; orbital window—the contralateral MCA and ipsilateral internal carotid artery siphons were detected.

Result interpretation: in the anterior circulation, the bilateral MCAs were the primary vessels assessed. The terminal internal carotid arteries or siphon segment of the internal carotid arteries served as alternative vessels; In the posterior circulation, the BA was the primary vessel for assessment, with the bilateral intracranial segments of the vertebral arteries as alternatives.

In the blood flow spectrum interpretation, oscillatory wave: presence of systolic forward and diastolic reverse blood flow signals within a single cardiac cycle, with a direction of flow index <0.8. Nail wave: early systolic unidirectional forward blood flow signals with a duration of <200 ms and a flow velocity of <50 cm/s. Absence of blood flow signals: no detectable blood flow. The test was performed twice with a 30 min interval between the assessments. If any of the aforementioned blood flow spectra were detected in both the anterior and posterior intracranial circulation, the TCD brain-death criteria were met.

FDG-PET/CT

The patients were evaluated by attending physicians to ensure that they could safely undergo out-of-intensive care unit (ICU) examinations, including the administration of pressor drugs and mechanical ventilation. Written informed consent was obtained from the patients or their next of kin for out-of-ICU and FDG-PET/CT examinations.

Patients fasted for at least 6 h before the examination, and no intravenous fluids containing glucose were administered during this period. The blood glucose levels were maintained at <8 mmol/L. Additionally, antiepileptic drugs and neuromuscular blockers were discontinued 15 h before the scan.

18F-FDG, provided by Shanghai Atomic Kexing Pharmaceutical Co., Ltd., was administered intravenously at a dose of 0.1 mCi/kg. The patients were positioned supine in a dimly lit, quiet, and odor-free room with their eyes closed. Following a 40 min uptake period, a brain scan was performed using a PET/CT system (GE Discovery Elite 690, USA). The PET scan was conducted in three-dimensional mode with a slice thickness of 3.75 mm. CT and PET resolutions were 512×512 and 256×256, respectively. The brain scan duration was 20 min.

Post-processing was conducted using a GE AW4.6 workstation (USA). CT images were displayed using a standard brain window, whereas PET images were set with a window width of 6 and a window level of 0. The photos were then visually assessed by a nuclear medicine expert with over 10 years of experience in PET/CT interpretation. Standardized uptake values (SUVs) in the regions of interest, including the cerebral cortex, periventricular white matter, basal ganglia, brainstem, cerebellum, and upper cervical spinal cord, were manually measured on PET images. The maximum SUV (SUV_max) was recorded for each region.

Case presentation

Case 1: hypoxic-ischemic encephalopathy

An 85-year-old man presented with a choking cough while eating duck meat. He subsequently developed confusion and unresponsiveness within 2 min and was admitted with a diagnosis of asphyxia, respiratory arrest, and successful cardiopulmonary resuscitation performed 20 min later. On admission, his Glasgow Coma Scale (GCS) score was 5. Clinical examination revealed a positive spontaneous respiratory provocation test with intact bilateral pupillary and corneal reflexes. On the 30th day of stable condition, the patient had a GCS score of 5 with brainstem reflexes present. The EEG exhibited a grade IV pattern, predominantly flat, with intermittent delta waves. TCD revealed weakened blood flow signals in both the anterior and posterior circulations.

FDG-PET/CT was performed to observe intracranial nerve injury in the patients through neuronal metabolism. The SUV_max values in the PET images for the frontal, parietal, temporal, and occipital lobes of the cerebral cortex were 4.6, 4.8, 4.2, and 5.0, respectively. In the periventricular white matter bilaterally, the SUV_max values were 1.5 and 0.8. The basal ganglia exhibited an SUV_max of 4.6. The SUV_max values for both thalami were 3.2 and 1.6. In the pons, the ventral and dorsal SUV_max values were 3.0 and 1.3, respectively, whereas the bulbar SUV_max was 2.8. The cerebellum had an SUV_max of 4.0, with a hypometabolic area on the right side measuring 1.5. The SUV_max of the upper cervical spinal cord was 1.9. Meninges were not visible. The SUVmax ranges (mean ± standard deviation) in different brain regions of healthy individuals, measured using the same method at our hospital, are as follows: frontal lobe (12.5±2.8), parietal lobe (11.7±2.7), temporal lobe (11.5±2.2), occipital lobe (15.5±4.5), periventricular white matter (3±0.7), basal ganglia (12.7±2.4), thalamus (12.2±2.3), pons (6.8±1.2), medulla oblongata (7.6±1.1), cerebellum (9.7±1.2), and upper cervical spinal cord (1.9±0.2).

The PET scan demonstrated bilateral reduced FDG uptake and hypometabolism, validating a diagnosis of hypoxic-ischemic brain injury, with a Coma Recovery Scale-Revised (CRS-R) score of 1, indicating coma. Various metabolic conditions in the two hemispheres and distinct brain regions contributed to determining the location and severity of brain injury (Figure 1).

Figure 1 FDG-PET/CT images of hypoxic-ischemic encephalopathy. Cross-sectional (A1), coronal (B1), and sagittal (C1) CT images. Cross-sectional (A2), coronal (B2), and sagittal (C2) images: FDG-PET/CT images demonstrating whole-brain hypometabolism. FDG-PET/CT, 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Case 2: BD/DNC without spinal reflex

A 46-year-old man was admitted with a sudden headache lasting 7 h and confusion lasting 3 h. He required endotracheal intubation, mechanical ventilation, and vasopressors to maintain his blood pressure. The patient exhibited loss of all five brainstem reflexes (pupillary, corneal, head-eye, vestibulo-ocular, and cough reflexes) and had a GCS score of 3. The patient was diagnosed with bilateral frontal lobe cerebral hemorrhage with ventricular rupture, spontaneous subarachnoid hemorrhage, and hydrocephalus. Clinical examination revealed a negative spontaneous respiratory provocation test, leading to the diagnosis of BD/DNC. Due to persistent inquiries and resistance from the family, confirmatory tests were conducted on the 99th day of stable condition. TCD revealed an absence of intracranial vascular flow. The EEG displayed flat waves, indicating no brain activity. An FDG-PET/CT scan was performed to provide additional evidence and alleviate the family’s concerns from the perspective of neuronal metabolism in the brain. The PET imaging revealed no tracer retention within the brain, with SUVs comparable to those of the surrounding air. The SUV_max of the upper cervical spinal cord was 0.9. The SUV_max of the meninges was 3.5, indicating concurrent meningitis. The CRS-R score was 0. Ultimately, BD/DNC was verified based on existing clinical examinations and confirmatory tests by two qualified physicians from the Department of Neurology and Critical Care Medicine of our hospital (Figure 2).

Figure 2 FDG-PET/CT images of a patient with BD/DNC. Cross-sectional (A1), coronal (B1), and sagittal (C1) CT images. Cross-sectional (A2), coronal (B2), and sagittal (C2) images: no glucose metabolism was observed in the brain parenchyma, and metabolic signals in and below the cervical spinal cord were weak. BD/DNC, brain death/death by neurologic criteria; FDG-PET/CT, 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Case 3: BD/DNC with abnormal motor responses

A 65-year-old man was admitted following a fall from a height. He was unconscious upon admission, dependent on mechanical ventilation, and required vasopressors to maintain blood pressure. All five brainstem reflexes were absent. The patient was diagnosed with a brain contusion, laceration, subdural hematoma, and brain swelling. The patient exhibited clinical signs of BD/DNC three hours after hospital admission. On the 54th day, he remained comatose, with absent brainstem reflexes (pupillary, corneal, head-eye, vestibulo-ocular, and cough reflexes), GCS score of 3, and fluctuating blood pressure requiring vasopressors. Spontaneous respiratory provocation tests revealed no respiratory drive. The TCD indicated no intracranial vascular flow, and the EEG displayed flat waves. Despite these findings, abnormal movements comparable to the Lazarus sign were observed in response to pain stimulation. The CRS-R score was 1. In the presence of abnormal clinical movements and resistance from the families, FDG-PET/CT imaging was performed (4,10), revealing no neuronal glucose metabolism in the brain, characterized by an “empty skull” phenomenon, while high signal intensity was observed in the upper cervical spinal cord. The SUV_max values for the upper cervical spinal cord and meninges were 3.2 and 4.2, respectively, which were associated with meningitis hypermetabolism. The diagnosis of BD/DNC was validated through clinical evaluation and additional testing by two physicians qualified in BD/DNC assessment from the Departments of Neurology and Critical Care Medicine at our hospital (Figure 3).

Figure 3 FDG-PET/CT images of a patient with BD/DNC. Cross-sectional (A1), coronal (B1), and sagittal (C1) CT images. Cross-sectional (A2), coronal (B2), and sagittal (C2) images: the images reveal the absence of neuronal glucose metabolism in the brain, indicating an “empty skull” phenomenon, while a high signal intensity was detected in the cervical spinal cord. BD/DNC, brain death/death by neurologic criteria; FDG-PET/CT, 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Case 4: BD/DNC with atypical limb movements

A 61-year-old female sustained a head injury in a car accident and was admitted to the emergency department with a GCS score of 3. She developed cardiac arrest but regained spontaneous circulation after 13 min of cardiopulmonary resuscitation. Upon ICU admission, the patient exhibited bilateral fixed mydriasis, absent light reflexes, and complete ventilator dependence. Blood pressure was maintained using high-dose norepinephrine and vasopressin. The spontaneous breathing experiment indicated no respiratory effort. On day 20 post-trauma, abnormal lower limb movements appeared, characterized by simultaneous knee flexion and dorsiflexion lasting 3–5 s after moderate abdominal and lower limb compression. These movements were non-reproducible within short intervals but could be reinduced after 10–15 min. Multiple TCD ultrasounds detected an absence of intracranial blood flow, and EEG demonstrated an isoelectric state. The CRS-R score was 1. Due to the possibility of spinally mediated limb movements and the family’s uncertainty, an FDG-PET/CT scan was conducted (4,10), revealing no neuronal glucose metabolism in the brain (“empty skull” sign, SUV_max =0), consistent with BD/DNC, while demonstrating increased metabolic activity in the cervical spinal cord (SUV_max =2.4) (Figure 4).

Figure 4 FDG-PET/CT images of a brain-dead patient with atypical limb movements. CT images in axial (A1), coronal (B1), and sagittal (C1) views. The corresponding FDG-PET/CT images (A2, B2, and C2) demonstrate absent neuronal glucose metabolism in the brain (“empty skull” sign) but increased metabolic activity in the cervical spinal cord. FDG-PET/CT, 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Discussion

The definition of BD/DNC varies internationally. The American Academy of Neurology (AAN) updated its evidence-based guidelines in 2023, which reaffirm the clinical diagnosis of BD/DNC based on three essential findings: coma with a known cause, absence of brainstem reflexes, and apnea. These criteria support the determination of irreversible loss of all functions of the entire brain, including the brainstem (4). Despite advances in medical technology, the diagnosis of BD/DNC in complex neurocritical cases cannot rely solely on clinical examination. According to the recent review by Suthar et al. (2024), multimodal neuroimaging continues to play a valuable ancillary role in the determination of BD/DNC, particularly in cases where components of the clinical examination or apnea testing cannot be completed (12).

To our knowledge, this is the first report on the use of FDG-PET/CT as a diagnostic aid in cases of BD/DNC accompanied by abnormal movement. In our study of four FDG-PET/CT cases involving brain injury, case 1 exhibited a positive spontaneous respiratory provocation test and retained bilateral pupillary and corneal reflexes. PET imaging revealed global cerebral hypometabolism, consistent with hypoxic-ischemic brain injury. Conversely, cases 2, 3, and 4 required ventilator support and vasopressors for blood pressure maintenance and had negative spontaneous respiratory provocation tests, with all five brainstem reflexes (pupillary, corneal, head-eye, vestibulo-ocular, and cough reflexes) absent. These patients were clinically diagnosed with BD/DNC. The TCD examination of cases 2, 3, and 4 did not reveal any intracranial vascular flow, while EEG indicated an electrically inactive state. BD/DNC was verified through clinical examination and additional tests by two qualified physicians from the Departments of Neurology and Critical Care Medicine of our hospital.

In cases 3 and 4, despite a clinical diagnosis of BD/DNC, the patient exhibited abnormal movements resembling the Lazarus sign (13) following stimulation. These movements caused some confusion in determining BD/DNC. Although these movements were initially interpreted as spinal reflexes and multiple TCD ultrasounds were performed, showing no intracranial blood flow signals, the family contested the diagnosis. We attempted to explain the presence of spinal reflexes from the perspective of neuronal metabolism in order to help the patient’s family accept the diagnosis of BD/DNC. The PET/CT imaging of both cases revealed a complete absence of glucose metabolism in the brain and brainstem, revealing an “empty skull” phenomenon consistent with BD/DNC (14,15). Cases 3 and 4 demonstrated a high signal intensity in the cervical spinal cord, which may account for the observed spinal reflexes. Case 2 exhibited weak signals in the cervical spinal cord with no clinically abnormal motor reflexes.

Brain-dead patients can exhibit spontaneous and reflexive movements, with reports indicating that up to 75% of such patients display involuntary, spontaneous, or reflexive movements before the implementation of the current criteria for death (16). A 5-year study involving over 100 patients, conducted using a standardized protocol, revealed that approximately half of the patients continued to exhibit spontaneous movements despite fulfilling the BD/DNC criteria. Toe flexion and fluctuation responses were the most prevalent at 53%, whereas the Lazarus sign, involving complex movements including head-turning, shoulder adduction, and upper limb flexion and extension, constituted 2% (17). Most abnormal movements in brain-dead patients are regarded as spinal reflexes, although their pathophysiological basis remains ambiguous. The data suggested no significant differences in age, gender, etiology of BD/DNC, or hemodynamic laboratory findings between patients with reflex movements and those lacking them (18). These abnormal movements can induce diagnostic ambiguity, challenging the conclusions drawn from standard clinical assessment. The “empty skull” phenomenon and higher signal intensity in the cervical spinal cord could explain this abnormal symptom. The observed spinal reflexes may reflect segmental neuronal activity or localized hypermetabolism in the spinal cord, which can persist despite the complete and irreversible loss of brain function due to severe head trauma.

Ancillary tests for confirming BD/DNC continue to be employed in clinical practice across different countries. Although TCD is extensively used for diagnosing BD/DNC, reports of false negatives in craniotomy cases and false positives in patients with persistent hypotension have been noted (7,8). Additionally, poor bone window penetration and hypothermia in patients can affect diagnostic accuracy. EEG is not ideal for assessing brainstem function, making concurrent use of SSEP advisable. Moreover, in specific scenarios, including when spontaneous or reflex movements are present or during venous-arterial extracorporeal membrane oxygenation support (when patients often experience hypotension and hypoperfusion), brainstem activity is overlooked by both the TCD and EEG (6). Conventional four-vessel cerebral angiography remains the gold standard among ancillary tests, as it provides direct evidence of cerebral circulatory arrest. However, it is an invasive procedure that requires the use of contrast agents, which can potentially affect kidney function. Interpretation of cerebral perfusion may be complicated by clinical factors such as decompressive craniectomy, ventricular shunting, or open fontanelles in infants (19). Nevertheless, angiography demands considerable technical proficiency to be reliably performed.

Radionuclide imaging can be classified into single-photon emission computed tomography (SPECT) and PET based on the mode and type of radioactive particles emitted. The procedure involves injecting radiopharmaceuticals that emit single photons or positrons into the body and imaging the distribution of these radionuclides using SPECT or PET equipment. This enables the analysis of organ function or metabolism, aiding in the diagnosis of diseases.

Compared to PET, SPECT was introduced earlier into clinical practice and remains widely used in BD/DNC determination across many countries. It is cost-effective, operationally convenient, and suitable for bedside evaluation. Indeed, in some hospital protocols, SPECT is considered superior to EEG and TCD due to its ability to demonstrate cerebral perfusion. However, its relatively lower spatial resolution and limited ability to assess brainstem or posterior fossa perfusion may restrict its use in some complex diagnostic scenarios (20). FDG is taken up by viable neurons, rendering it a more sensitive indicator for neuronal metabolism or BD/DNC. PET also offers higher spatial resolution, is more effective for brainstem functional imaging, requires less imaging time, exposes patients to lower radiation, and is considered more advanced than SPECT (21). PET combined with magnetic resonance multimodal imaging provides greater advantages over SPECT combined with CT, especially in assessing functional abnormalities in complex brain regions, including the cerebellum, midbrain, and medulla oblongata (22). Moreover, PET has demonstrated faster market growth in recent years and holds potential as a gold standard ancillary diagnostic tool (23,24).

Consequently, FDG-PET/CT is an essential tool for BD/DNC confirmation, clearly visualizing metabolism in both the posterior fossa and the brainstem. When neuromuscular reflexes exist, clinical examinations are inconclusive, and families express resistance or uncertainty, FDG-PET/CT can identify brain activity and assist in excluding BD/DNC (15,19). However, FDG-PET/CT is currently not part of the ancillary testing methods recommended by the updated 2023 AAN guidelines for the determination of BD/DNC. Its limitations include the short half-life of radionuclides and the limited availability of PET/CT equipment and nuclear radiology technicians in some hospitals. Moreover, FDG-PET/CT requires well-controlled blood glucose levels. The risks associated with transport, including potential cardiac arrest, full ventilator dependence, and detachment of various catheters due to movement, are especially concerning in critically ill patients with hemodynamic instability.

Currently, there is limited literature on the application of FDG-PET/CT for diagnosing BD/DNC, with a lack of clinical trials. Well-designed studies are required to evaluate its sensitivity and specificity relative to existing diagnostic tools, including digital subtraction angiography, TCD, SPECT, and EEG. These investigations provide critical evidence to support the clinical application of FDG-PET/CT.

Conclusions

Although 18F-FDG-PET/CT is not included in current diagnostic guidelines for BD/DNC, our findings suggest that it may provide helpful complementary data in complex clinical scenarios, such as those with persistent spinal reflexes. FDG-PET/CT offers high-resolution functional imaging of brainstem regions, which may aid interpretation in selected cases. Further prospective studies are warranted to assess the sensitivity and specificity of FDG-PET/CT compared to established ancillary tests.

Acknowledgments

None.

Footnote

Funding: This study was supported by Zhejiang Provincial Basic and Public Welfare Research Program (No. LGC20H090001 to K.C.), Zhejiang Province Medical and Health Science and Technology Plan Project (No. 2019PY091 to K.C.), National Key Research and Development Program of China (No. 2022YFE0141300 to H.D.), Key Project Zhejiang Provincial Natural Science Foundation (No. Z21H170001 to H.D.) and Major Project of Taizhou Enze Medical Center (No. 2022EZZD05 to G.W.).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1134/coif). K.C. reports funding from Zhejiang Provincial Basic and Public Welfare Research Program (No. LGC20H090001), Zhejiang Province Medical and Health Science and Technology Plan Project (No. 2019PY091). H.D. reports funding from National Key Research and Development Program of China (No. 2022YFE0141300), Key Project Zhejiang Provincial Natural Science Foundation (No. Z21H170001). G.W. reports funding from Major Project of Taizhou Enze Medical Center (No. 2022EZZD05). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Helsinki Declaration and its subsequent amendments. This study was approved by the Ethics Review Board of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Approval No. K20190602). Written informed consent was obtained from the patients or their next of kin for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. A definition of irreversible coma. Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. JAMA 1968;205:337-40.
2. National Health Commission Brain Injury Quality Control and Evaluation Center, Neurocritical Care Collaboration Group of the Chinese Medical Association Neurology Branch, Neurocritical Care Committee of the Neurology Branch of the Chinese Medical Doctor Association. Criteria and practical guidance for determination of brain death in adults in China (2nd edition). National Medical Journal of China 2019;99:1288-92.
3. Brain Injury Evaluation Quality Control Center of National Health Commission. Criteria and practical guidance for determination of brain death in children. Zhonghua Er Ke Za Zhi 2019;57:331-5. [Crossref] [PubMed]
4. Greer DM, Kirschen MP, Lewis A, Gronseth GS, Rae-Grant A, Ashwal S, Babu MA, Bauer DF, Billinghurst L, Corey A, Partap S, Rubin MA, Shutter L, Takahashi C, Tasker RC, Varelas PN, Wijdicks E, Bennett A, Wessels SR, Halperin JJ. Pediatric and Adult Brain Death/Death by Neurologic Criteria Consensus Guideline. Neurology 2023;101:1112-32. [Crossref] [PubMed]
5. Spears W, Mian A, Greer D. Brain death: a clinical overview. J Intensive Care 2022;10:16. [Crossref] [PubMed]
6. Wiles MD. Ancillary tests to support the diagnosis of death using neurological criteria: certainty in uncertain times? Anaesthesia 2023;78:816-9. [Crossref] [PubMed]
7. Chang JJ, Tsivgoulis G, Katsanos AH, Malkoff MD, Alexandrov AV. Diagnostic Accuracy of Transcranial Doppler for Brain Death Confirmation: Systematic Review and Meta-Analysis. AJNR Am J Neuroradiol 2016;37:408-14. [Crossref] [PubMed]
8. Ducrocq X, Braun M, Debouverie M, Junges C, Hummer M, Vespignani H. Brain death and transcranial Doppler: experience in 130 cases of brain dead patients. J Neurol Sci 1998;160:41-6. [Crossref] [PubMed]
9. Huang CX, Li YH, Lu W, Huang SH, Li MJ, Xiao LZ, Liu J. Positron emission tomography imaging for the assessment of mild traumatic brain injury and chronic traumatic encephalopathy: recent advances in radiotracers. Neural Regen Res 2022;17:74-81. [Crossref] [PubMed]
10. Greer DM, Shemie SD, Lewis A, Torrance S, Varelas P, Goldenberg FD, et al. Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project. JAMA 2020;324:1078-97. [Crossref] [PubMed]
11. Lewis A, Bakkar A, Kreiger-Benson E, Kumpfbeck A, Liebman J, Shemie SD, Sung G, Torrance S, Greer D. Determination of death by neurologic criteria around the world. Neurology 2020;95:e299-309. [Crossref] [PubMed]
12. Suthar PP, Jhaveri MD, Kounsal A, Pierce LD, Singh JS. Role of Clinical and Multimodality Neuroimaging in the Evaluation of Brain Death/Death by Neurologic Criteria and Recent Highlights from 2023 Updated Guidelines. Diagnostics (Basel) 2024;14:1287. [Crossref] [PubMed]
13. Beckmann Y, Çiftçi Y, Incesu TK, Seçil Y, Akhan G. Spinal reflexes in brain death. Acta Neurol Belg 2014;114:303-6. [Crossref] [PubMed]
14. Meyer MA. Evaluating brain death with positron emission tomography: case report on dynamic imaging of 18F-fluorodeoxyglucose activity after intravenous bolus injection. J Neuroimaging 1996;6:117-9. [Crossref] [PubMed]
15. Yousefi-Koma A, Sadegh-Beigee F, Ghorbani F, Mirbahaeddin K, Aghahosseini F, Alibeigi E, Jarrah N. Brain Death Confirmation by 18F-FDG PET/CT: A Case Series. Exp Clin Transplant 2023;21:756-63. [Crossref] [PubMed]
16. Wijdicks EF, Varelas PN, Gronseth GS, Greer DMAmerican Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2010;74:1911-8. [Crossref] [PubMed]
17. Saposnik G, Mauriño J, Saizar R, Bueri JA. Undulating toe movements in brain death. Eur J Neurol 2004;11:723-7. [Crossref] [PubMed]
18. Saposnik G, Maurino J, Saizar R, Bueri JA. Spontaneous and reflex movements in 107 patients with brain death. Am J Med 2005;118:311-4. [Crossref] [PubMed]
19. Spinello IM. Brain Death Determination. J Intensive Care Med 2015;30:326-37. [Crossref] [PubMed]
20. Derlin T, Weiberg D. 99mTc-HMPAO perfusion SPECT/CT in the diagnosis of brain death. Nucl Med Rev Cent East Eur 2016;19:22-3. [Crossref] [PubMed]
21. Willowson KP, Bailey DL. Evolving SPECT-CT technology. Br J Radiol 2024; Epub ahead of print. [Crossref]
22. Kas A, Rozenblum L, Pyatigorskaya N. Clinical Value of Hybrid PET/MR Imaging: Brain Imaging Using PET/MR Imaging. Magn Reson Imaging Clin N Am 2023;31:591-604. [Crossref] [PubMed]
23. Crișan G, Moldovean-Cioroianu NS, Timaru DG, Andrieș G, Căinap C, Chiș V. Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade. Int J Mol Sci 2022;23:5023. [Crossref] [PubMed]
24. Bartlett EA, Lesanpezeshki M, Anishchenko S, Shkolnik I, Ogden RT, Mann JJ, Beylin D, Miller JM, Zanderigo F. Dynamic Human Brain Imaging with a Portable PET Camera: Comparison to a Standard Scanner. J Nucl Med 2024;65:320-6. [Crossref] [PubMed]