Mitochondrial networks in cardiac myocytes under oxidative stress show collective (cluster) behavior through synchronization of their inner membrane potentials (ΔΨ _m ). However, it is unclear whether the oscillation frequency and coupling strength between individual mitochondria affect the size of the cluster and vice versa. We used the wavelet transform and developed advanced signal processing tools that allowed us to capture individual mitochondrial ΔΨ _m oscillations in cardiac myocytes and examine their dynamic spatio-temporal properties. Heterogeneous frequency behavior prompted us to sort mitochondria according to their frequencies. Signal analysis of the mitochondrial network showed an inverse relationship between cluster size and cluster frequency as well as between cluster amplitude and cluster size. High cross-correlation coefficients between neighboring mitochondria clustered longitudinally along the myocyte striations, indicated anisotropic communication between mitochondria. Isochronal mapping of the onset of myocyte-wide ΔΨ _m depolarization further exemplified heterogeneous ΔΨ _m among mitochondria. Taken together, the results suggest that frequency and amplitude modulation of clusters of synchronized mitochondria arises by means of strong changes in local coupling between neighboring mitochondria.

Distal symmetric diabetic polyneuropathy (DPN) is one of the most severe complications of diabetes, affecting approximately 200 million patients worldwide, with increasing prevalence leading to high morbidity and rising health care costs.¹ Although the exact metabolic processes underlying DPN are still uncertain, several clinical and serologic risk factors for developing DPN, such as obesity, hypertension, hyperglycemia, dyslipidemia, and a decrease in renal function, have been identified in clinical studies.^2-4 The poor outcomes after adjusting serum glucose levels in patients with type 2 diabetes (T2D) compared with type 1 diabetes (T1D) suggest that risk factors other than hyperglycemia might play an important role in the development of DPN.^3,5 An in vitro study⁶ found that, in samples from patients with T2D and DPN, lipid composition of Schwann cells is altered compared with samples from control individuals without DPN. To date, it has not been possible to visualize those alterations in the nerve’s microstructure in vivo. Inpatient magnetic resonance neurography (MRN) at 3.0 T is a noninvasive method that allows for an exact qualitative and quantitative analysis of nerve damage in different neuropathies.^7-9 Recent results from an MRN study¹⁰ in patients with DPN have shown that a decrease in serum high-density lipoprotein cholesterol (HDL-C) levels is associated with an increase in fat-equivalent lesions of the sciatic nerve and an increase in clinical symptom severity. These nerve lesions also occurred more frequently in patients with T2D compared with patients with T1D.¹⁰ The exact role of cholesterol metabolism in the development of DPN, however, is unknown, and it has not yet been determined whether lowering serum cholesterol levels in patients with T2D has a positive influence on the course of T2D DPN.¹¹ Some clinical studies^11,12 have found that a lowering of serum cholesterol levels had positive effects on the course of DPN that were mainly attributed to lowering low-density lipoprotein cholesterol (LDL-C) levels and to anti-inflammatory and antioxidative effects of statin treatment. However, low serum cholesterol levels are associated with neuropathic symptoms and impair nerve regeneration after axonal damage in neurons of the central and peripheral nervous systems.^13-17 This association was mainly attributed to an insufficient supply of cholesterol to neurite tips and adjacent Schwann cells of regenerating axons as a consequence of a decrease in lipoproteins.^14,18-21 With regard to emerging therapies, such as protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors that promote an aggressive lowering of total serum cholesterol levels,¹⁶ it is crucial to understand whether a decrease in total serum cholesterol and LDL-C levels is beneficial or potentially harmful for patients with T2D with DPN.

The discovery of the glymphatic system has revolutionized our understanding of brain physiology, particularly in waste clearance and fluid dynamics within the central nervous system. This pathway, essential for nutrient distribution and waste removal, operates predominantly during sleep and has been implicated in neurodegenerative diseases like Alzheimer's and Parkinson's. Recent advances in non-invasive MRI techniques, including diffusion tensor imaging along the perivascular space (DTI-ALPS), perivascular space (PVS) analysis, and free water (FW) indices, have improved our ability to study glymphatic function and its alterations in disease states. This review discusses the glymphatic system's ultrastructure, physiology, and the latest imaging methods to assess this critical pathway. We highlight how these non-invasive MRI techniques can enhance the understanding of glymphatic function in health and disease, with a focus on neurodegenerative conditions. By integrating insights from current research, this review underscores the diagnostic and therapeutic implications of glymphatic dysfunction. Understanding these mechanisms can pave the way for novel strategies to enhance waste clearance and improve neurological health, offering potential benefits for early diagnosis and intervention in neurodegenerative diseases.

In patients with diabetes, 3-T MR neurography showed the extent of hyperintense T2 lesions in the sciatic nerve was greater in patients with painful diabetic polyneuropathy than in those without pa... Background The pathophysiologic mechanisms underlying painful symptoms in diabetic polyneuropathy (DPN) are poorly understood. They may be associated with MRI characteristics, which have not yet be...

Clinical studies have suggested that changes in peripheral nerve microcirculation may contribute to nerve damage in diabetic polyneuropathy (DN). High-sensitivity troponin T (hsTNT) assays have been recently shown to provide predictive values for both cardiac and peripheral microangiopathy in type 2 diabetes (T2D). This study investigated the association of sciatic nerve structural damage in 3 Tesla (3T) magnetic resonance neurography (MRN) with hsTNT and N-terminal pro-brain natriuretic peptide serum levels in patients with T2D. MRN at 3T was performed in 51 patients with T2D (23 without DN, 28 with DN) and 10 control subjects without diabetes. The sciatic nerve’s fractional anisotropy (FA), a marker of structural nerve integrity, was correlated with clinical, electrophysiological, and serological data. In patients with T2D, hsTNT showed a negative correlation with the sciatic nerve’s FA (r = −0.52, P < 0.001), with a closer correlation in DN patients (r = −0.66, P < 0.001). hsTNT further correlated positively with the neuropathy disability score (r = 0.39, P = 0.005). Negative correlations were found with sural nerve conduction velocities (NCVs) (r = −0.65, P < 0.001) and tibial NCVs (r = −0.44, P = 0.002) and amplitudes (r = −0.53, P < 0.001). This study is the first to show that hsTNT is a potential indicator for structural nerve damage in T2D. Our results indirectly support the hypothesis that microangiopathy contributes to structural nerve damage in T2D.