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Contrast-Free FLIM Reveals Metabolic Changes in Pathological Islets of Langerhans
Polina Ermakova1, Alena Kashirina1, Irina Kornilova1
1Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Pl., 603005 Nizhny Novgorod, Russia.
Insights
Fluorescence Lifetime Imaging Microscopy (FLIM) can identify specific metabolic changes in pancreatic islet cells. These changes may help diagnose diabetes and other pancreatic pathologies.
Area of Science:
- Biomedical Optics
- Metabolic Imaging
- Pancreatic Pathophysiology
Background:
- Pancreatic islet cells are crucial for metabolic regulation.
- Assessing islet cell health and metabolism is vital for diagnosing and managing diabetes and other pancreatic diseases.
- Current diagnostic methods for pancreatic pathologies can be invasive or lack specificity.
Purpose of the Study:
- To identify key Fluorescence Lifetime Imaging Microscopy (FLIM) parameters indicative of pancreatic pathologies.
- To evaluate the potential of FLIM for diagnosing islet cell dysfunction and recovery.
- To correlate FLIM findings with established histological and immunohistochemical data.
Main Methods:
- Measurement and analysis of NAD(P)H lifetime parameters (τm, τ1, τ2, α1, α2, α1/α2) in islet cells from animal models (rats, pigs) and human subjects.
- Utilized streptozotocin-induced diabetes mellitus (DM) in animals and human cohorts with chronic pancreatitis, type 2 diabetes (T2D), and pancreatic ductal adenocarcinoma (PDAC).
- Validation of FLIM data using immunohistochemistry (IHC) and standard histological studies.
Main Results:
- Identified distinct FLIM parameter alterations in islet cells from STZ-induced DM and human T2D/chronic pancreatitis: decreased τm and α2, increased α1/α2 compared to non-pathological controls.
- Observed reverse trends or no significant differences in these parameters for islet cells from PDAC and chronic pancreatitis patients relative to controls.
- Demonstrated consistency in FLIM parameter changes across different species and human pathologies.
Conclusions:
- Specific FLIM parameters of NAD(P)H metabolism are significantly altered in pathological islet cells.
- FLIM offers a potential minimally invasive, non-contrast method for diagnosing pancreatic pathologies, including diabetes and pancreatitis.
- Further research into FLIM applications could enhance early detection and monitoring of islet cell health.
Abstract:
FLIM (Fluorescence Lifetime Imaging Microscopy) is a powerful tool that could be used in the future to diagnose islet cell recovery after therapy. The identification of appropriate FLIM parameters is required to determine islet quality and islet cell metabolism throughout the organ under various conditions of insulin deficiency. The aim of the work was to identify key FLIM parameters, changes of which are characteristic of pancreatic pathologies. The τm, τ1, τ2, α1, α2 and α1/α2 of free and bound forms of NAD(P)H of the islet cells of animals (rats and pigs) and of humans with and without pathologies were measured and analyzed. The data were confirmed by IHC and histological studies. We identified three FLIM parameters in islet cells from animals with streptozotocin (STZ)-induced diabetes mellitus (DM) and from humans with chronic pancreatitis + type 2 diabetes (T2D), which differ in the same way: τm and α2 take lower values compared to the nonpathological islet cells, while α1/α2 takes higher values. In islet cells from patients with adenocarcinoma (PDAC) and chronic pancreatitis, these parameters had reverse tendency relative to the norm or did not differ. Thus, minimally invasive and non-contrast FLIM methods may, in the future, be used to diagnose pathological islet cells.
