Shixie Jiang

Delirium is a complex neuropsychiatric syndrome with multifactorial pathophysiology, encompassing a wide range of neuropsychiatric symptoms, and its management remains a significant challenge in critical care. Although often managed with antipsychotics, like haloperidol, current research has predominantly focused on dopamine dysregulation as the primary driver of delirium, overlooking its broader neuroanatomical and neurochemical underpinnings. This has led to a majority of research focusing on haloperidol as a treatment for intensive care unit (ICU) delirium. Our review critically evaluates the role of haloperidol in ICU delirium management, particularly in light of recent large-scale randomized controlled trials (RCTs) that have primarily focused on delirium-free days and mortality as the primary endpoints. These studies highlight an limited understanding of the true nature of delirium treatment, which requires a broader, neuropsychiatric approach. We argue that future research should shift focus to neuropsychiatric symptoms such as agitation and psychosis and explore the clinical and functional benefits of reducing these distressing symptoms. Additionally, the stratification of delirium by subtypes and etiology, the enhancement of detection tools, and the adoption of multi-intervention and multi-disciplinary care approaches should be prioritized. Despite the methodological flaws in these studies, the findings support the safety of haloperidol in the ICU setting, with minimal risk of adverse events, particularly cardiac and neuropsychiatric. Moving forward, delirium research must integrate modern neuroscientific understanding and adopt more multi-disciplinary input and nuanced, patient-centered approaches to truly advance clinical care and outcomes.

Sepsis is a life-threatening syndrome consisting of physiological, pathological, and biochemical abnormalities induced by infection which continues to be a major public health burden. It remains one of the most common reasons for intensive care unit (ICU) admission. Delirium precipitated by sepsis in the intensive care setting is one of its most common neuropsychiatric complications that leads to prolonged hospitalization, increased mortality, and an increased risk of incident dementia. Understanding the pathophysiology and neurobiological mechanisms of sepsis-associated delirium is difficult; neuroimaging biomarkers are lacking due to difficulties with imaging critically ill patients. Optical imaging techniques, including near-infrared spectroscopy and diffuse optical tomography are potentially promising approaches for investigating this pathophysiology due to their portability and high spatiotemporal resolution. In this review, we examine the emergence of optical neuroimaging techniques for the study of sepsis-associated delirium in the ICU and how they can further advance our knowledge and lead to the development of improved preventative, predictive, and therapeutic strategies.

INTRODUCTION: Delirium is associated with mortality and new onset dementia, yet the underlying pathophysiology remains poorly understood. Development of imaging biomarkers has been difficult given the challenging nature of imaging delirious patients. Diffuse optical tomography (DOT) offers a promising approach for investigating delirium given its portability and three‐dimensional capabilities.METHODS: Twenty‐five delirious and matched non‐delirious patients (n = 50) were examined using DOT, comparing cerebral oxygenation and functional connectivity in the prefrontal cortex during and after an episode of delirium.RESULTS: Total hemoglobin values were significantly decreased in the delirium group, even after delirium resolution. Functional connectivity between the dorsolateral prefrontal cortex and dorsomedial prefrontal cortex was strengthened post‐resolution compared to during an episode; however, this relationship was still significantly weaker compared to controls.DISCUSSION: These findings highlight DOT's potential as an imaging biomarker to measure impaired cerebral oxygenation and functional dysconnectivity during and after delirium. Future studies should focus on the role of cerebral oxygenation in delirium pathogenesis and exploring the etiological link between delirium and dementias.Highlights: We developed a portable diffuse optical tomography (DOT) system for bedside three‐dimensional functional neuroimaging to study delirium in the hospital. We implemented a novel DOT task‐focused seed‐based correlation analysis. DOT revealed decreased cerebral oxygenation and functional connectivity strength in the delirium group, even after resolution of delirium.

Functional neuroimaging studies of neuropsychiatric disorders and cognitive impairment are commonly conducted in the clinic setting but less so in the acutely medically ill while hospitalized. This is largely due to technical and logistical limitations, given the lack of portable devices with high spatial and temporal resolutions. This exploratory study reports on the development and implementation of a novel diffuse optical tomography (DOT) system that can be employed for bedside three-dimensional functional neuroimaging. To test this portable DOT system, our protocol included a task-based sequence involving the Months Backwards Test with imaging centered on the bilateral prefrontal cortex. Fifteen subjects were recruited from intensive care units and the general wards of a single tertiary academic hospital and included in our final analysis. Volumetric hemoglobin analyses of the dorsolateral prefrontal cortex (DLPFC) and dorsomedial prefrontal cortex (DMPFC) were reliably captured in all our subjects. The peak value was calculated to be 3.36 µM and 0.74 µM for oxygenated-hemoglobin (HbO) and total-hemoglobin (HbT) (p < 0.042, [HbT]), respectively. The standard error was calculated to be 4.58 uM and 3.68 uM for (HbO) and (HbT). We additionally developed a seed-based correlation analysis to demonstrate the capability of DOT in studying functional connectivity. The right DLPFC was found to be moderately associated with the left DLPFC in all our subjects (r = 0.656). The DMPFC was observed to be associated with the left DLPFC but less so (r = 0.273) at the group level. Overall, the contribution of left-to-right DLPFC connectivity was significantly higher than left DLPFC to DMPFC in our group (p = 0.012). Future studies should investigate the potential of such a DOT system in the research of neuropsychiatric and neurocognitive disorders within the hospital to study different types of mechanisms, pathophysiology, and interventions that occur acutely and can advance our knowledge of these disorders.

Delirium persists as the most common neuropsychiatric syndrome among medically ill hospitalized patients, yet its neural mechanisms remain poorly understood. The development of neuroimaging biomarkers has been difficult primarily due to the complexities of imaging patients experiencing delirium. Optical imaging techniques, including near-infrared spectroscopy (NIRS) and diffuse optical tomography (DOT), offer promising avenues for investigating delirium’s pathophysiology. These modalities uniquely stand out for delirium exploration due to their blend of spatiotemporal resolution, bedside applicability, cost-effectiveness, and potential for real-time monitoring. In this review, we examine the emergence of optical imaging modalities and their pioneering utility in delirium research. With further investment and research efforts, they will become instrumental in our understanding of delirium’s pathophysiology and the development of preventive, predictive, and therapeutic strategies.

This study aims to explore the feasibility of fine-needle aspiration biopsy (FNAB) under dual modal photoacoustic tomography(PAT)/ultrasound (US) imaging. A total of 25 patients who have thyroid nodules with thyroid imaging reporting and data system (TIRADS) 3 and 4 (malignant risk Bethesda system for reporting thyroid cytopathology diagnostic category (DC) I: 4%(1/25); DC II: 12% (3/25); DC III: 20% (5/25); DC IV: 8% (2/25); DC V: 32% (8/25); and DC VI: 24% (6/25). The DC I nodule exhibited inadequate cytology and had structural characteristic of predominant calcifications in PAT/US mapping. The DC V-VI nodules showed lower photoacoustic (PA) signals compared to the DC I-IV nodules. Regions with a high PA signal demonstrated a significant number of erythrocytes in FNAB cytology. Moreover, nodules with microcalcifications did not show a significant difference compared to their surroundings in the PA signal, while nodules with macrocalcifications gave higher PA signals compared to their surroundings. The conclusions are as follows: combining US with PAT can evaluate the structure and function of thyroid nodules in vivo. This study demonstrates that dual modal PAT/US imaging has the potential to be an effective clinical tool to guide FNAB of thyroid nodules.