US-12622631-B2 - Systems and methods for quantifying retrograde trans-synaptic degeneration

Abstract

A method for quantifying retrograde trans-synaptic degeneration (rTSD) in a patient includes receiving optical coherence tomography (OCT) image data associated with a left retina and a right retina of the patient. The method further includes analyzing the OCT image data to determine a thickness of one or more retinal layers of the left retina and one or more retinal layers of the right retina. The method further includes, based at least in part on the determined thicknesses, determining a value of an rTSD index that is indicative of a level of rTSD in the patient. The rTSD index can be based at least in part on the thicknesses of retinal layers connected to a left optic radiation of the patient versus the thicknesses of retinal layers connected to a right optic radiation of the patient.

Inventors

• Omar Al-Louzi
• Pascal Sati

Assignees

• CEDARS-SINAI MEDICAL CENTER

Dates

Publication Date

20260512

Application Date

20240421

Claims (20)

1. 1 . A method for quantifying retrograde trans-synaptic degeneration (rTSD) in a patient, the method comprising: receiving optical coherence tomography (OCT) image data associated with a left retina and a right retina of the patient; analyzing the OCT image data to determine a thickness of one or more retinal layers of the left retina and one or more retinal layers of the right retina; and based at least in part on the determined thicknesses, determining a value of an rTSD index that is indicative of a level of rTSD in the patient, the rTSD index value being based on a ratio between (i) a combined thickness of one or more retinal layers of the left retina connected to a left optic radiation of the patient and one or more retinal layers of the right retina connected to the left optic radiation of the patient, and (ii) a combined thickness of one or more retinal layers of the left retina connected to a right optic radiation of the patient and one or more retinal layers of the right retina connected to the right optic radiation of the patient.
2. 2 . The method of claim 1 , wherein a cause of the rTSD is a lesion in the left optic radiation of the patient, the right optic radiation of the patient, or both.
3. 3 . The method of claim 2 , wherein the lesion is a paramagnetic rim lesion, a central vein sign+(CVS+)lesion, or both.
4. 4 . The method of claim 1 , wherein an absolute value of the rTSD index is indicative of a magnitude of the rTSD in one hemisphere of a brain of the patient relative to an opposing hemisphere of the brain of the patient.
5. 5 . The method of claim 1 , wherein: the one or more retinal layers of the left retina connected to the left optic radiation of the patent includes a left temporal ganglion cell and inner plexiform layer (right temporal GCIPL); the one or more retinal layers of the right retina connected to the left optic radiation of the patient includes a right nasal GCIPL; the one or more retinal layers of the left retina connected to the right optic radiation of the patient includes a left nasal GCIPL; and the one or more retinal layers of the right retina connected to the right optic radiation of the patient a right temporal GCIPL.
6. 6 . The method of claim 5 , wherein the rTSD index is given by rTSD index = ( left ⁢ temporal ⁢ GCIPL ⁢ thickness + right ⁢ nasal ⁢ GCIPL ⁢ thickness right ⁢ temporal ⁢ GCIPL ⁢ thickness + left ⁢ nasal ⁢ GCIP ⁢ thickness - 1 ) × 100.
7. 7 . The method of claim 6 , wherein the value of the rTSD index relative to 0 is indicative of whether a cause of the rTSD is located in a left hemisphere of a brain of the patient or a right hemisphere of the brain of the patient.
8. 8 . The method of claim 7 , wherein the index value being greater than 0 indicates that a cause of the rTSD is located in a left hemisphere of a brain of the patient, and wherein the index value being less than 0 indicates that a cause of the rTSD is located in a right hemisphere of a brain of the patient.
9. 9 . The method of claim 1 , wherein the one or more retinal layers connected to the left optic radiation of the patient includes one or more retinal layers located on a left side of the left retina and a left side of the right retina, and wherein the one or more retinal layers connected to the right optic radiation of the patient includes one or more retinal layers located on a right side of the right retina and a right side of the left retina.
10. 10 . The method of claim 1 , wherein analyzing the OCT image data includes segmenting the left retina and the right retina within the OCT image data to identify the one or more retinal layers of the left retina and the one or more retinal layers of the right retina.
11. 11 . The method of claim 1 , wherein: the one or more retinal layers of the right retina connected to the left optic radiation of the patient includes a right nasal temporal ganglion cell and inner plexiform layer (right temporal GCIPL); the one or more retinal layers of the right retina connected to the right optic radiation of the patient includes a right temporal GCIPL; the one or more retinal layers of the left retina connected to the left optic radiation of the patient includes a left temporal GCIPL; and the one or more retinal layers of the left retina connected to the right optic radiation of the patient a left nasal GCIPL.
12. 12 . The method of claim 11 , wherein the one or more retinal layers connected to the left optic radiation of the patient includes one or more retinal layers located on a left side of the left retina and a left side of the right retina, and wherein the one or more retinal layers connected to the right optic radiation of the patient includes one or more retinal layers located on a right side of the right retina and a right side of the left retina.
13. 13 . The method of claim 11 , wherein the rTSD index is given by rTSD index = rTSD index = ( ( ( right ⁢ nasal ⁢ GCIPL ⁢ thickness right ⁢ temporal ⁢ GCIPL ⁢ thickness + left ⁢ temporal ⁢ GCIPL ⁢ thickness left ⁢ nasal ⁢ GCIPL ⁢ thickness ) × 1 2 ) - 1 ) × 100.
14. 14 . The method of claim 13 , wherein the value of the rTSD index relative to 0 is indicative of whether a cause of the rTSD is located in a left hemisphere of a brain of the patient or a right hemisphere of the brain of the patient.
15. 15 . The method of claim 14 , wherein the index value being greater than 0 indicates that a cause of the rTSD is located in a left hemisphere of a brain of the patient, and wherein the index value being less than 0 indicates that a cause of the rTSD is located in a right hemisphere of a brain of the patient.
16. 16 . The method of claim 11 , wherein a cause of the rTSD is a lesion in the left optic radiation of the patient, the right optic radiation of the patient, or both.
17. 17 . The method of claim 16 , wherein the lesion is a paramagnetic rim lesion, a central vein sign+(CVS+) lesion, or both.
18. 18 . The method of claim 11 , wherein an absolute value of the rTSD index is indicative of a magnitude of the rTSD in one hemisphere of a brain of the patient relative to an opposing hemisphere of the brain of the patient.
19. 19 . The method of claim 11 , wherein analyzing the OCT image data includes segmenting the left retina and the right retina within the OCT image data to identify the one or more retinal layers of the left retina and the one or more retinal layers of the right retina.
20. 20 . A method for quantifying retrograde trans-synaptic degeneration (rTSD) in a patient, the method comprising: receiving optical coherence tomography (OCT) image data associated with a left retina and a right retina of the patient; analyzing the OCT image data to determine a thickness of one or more retinal layers of the left retina and one or more retinal layers of the right retina; and based at least in part on the determined thicknesses, determining a value of an rTSD index that is indicative of a level of rTSD in the patient, the rTSD index value being based on a sum of (i) a ratio between a thickness of one or more retinal layers of the right retina connected to a left optic radiation of the patient and one or more retinal layers of the right retina connected to a right optic radiation of the patient and (ii) a ratio between a thickness of one or more retinal layers of the left retina connected to the left optic radiation of the patient and one or more retinal layers of the left retina connected to the right optic radiation of the patient.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Patent Application. No. 63/497,698, filed Apr. 21, 2023, which is hereby incorporated by reference herein in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with Government support under Grant No. HT9425-23-1-0571 awarded by the Department of Defense. The Government has certain rights in the invention. TECHNICAL FIELD The present disclosure relates generally to systems and methods for quantifying retrograde trans-synaptic degeneration (rTSD), and more particularly, to systems and methods for quantifying rTSD based on the thicknesses of various retinal cell layers. BACKGROUND Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disorder of the central nervous system, and one of the most common causes of neurological disability in young adults with rising incidence and economic burden. Despite significant advances in the understanding MS pathobiology, there are considerable gaps in the ability to accurately predict or halt disability progression in MS, especially in the progressive forms of the disease where effective therapies are extremely limited and show benefit primarily in the early stages when there is concomitant active inflammation. Therefore, there is a need to develop accurate biomarkers of neurodegeneration and disability progression in MS for use as outcome measures in clinical trials of neuroprotective therapies. Neuroaxonal degeneration is one of the main drivers of permanent clinical disability in MS. The exact mechanisms contributing to widespread neurodegeneration, however, remain elusive and may harbor the key to understanding relapse-independent disability progression experienced by patients with MS (pwMS). Transsynaptic degeneration plays an important role in propagating neuronal loss in many neurological disorders by setting off a chain of neuronal degeneration anterograde and retrograde to the neuroaxonal unit directly affected, which may play a role in exacerbating relapse-independent disability in pwMS over time. The visual pathway lends itself readily to the investigation of trans-synaptic degeneration given an intricate structure-function correlation. Recent advances in optical coherence tomography (OCT), a reproducible, noninvasive retinal imaging technique, have enabled precise quantification of retinal layer thickness and assessment of the pre-geniculate visual pathway. When coupled with magnetic resonance imaging (MRI) of the post-geniculate visual pathway, this allows the in vivo investigation of mechanisms driving neurodegeneration across visual pathway synapses. Prior investigations have demonstrated that retrograde trans-synaptic degeneration (rTSD) of the retina occurs in response to some, but—importantly—not all MS lesions in the posterior visual pathway. The specific characteristics of MS lesions that promote trans-synaptic neuronal loss, versus those that do not, are poorly understood. Thus, new systems and methods for quantifying rTSD are needed. SUMMARY According to some implementations of the present disclosure, a method for quantifying retrograde trans-synaptic degeneration (rTSD) in a patient comprises receiving optical coherence tomography (OCT) image data associated with a left retina and a right retina of the patient. The method further comprises analyzing the OCT image data to determine a thickness of one or more retinal layers of the left retina and one or more retinal layers of the right retina. The method further comprises, based at least in part on the determined thicknesses, determining a value of an rTSD index that is indicative of a level of rTSD in the patient. In some implementations, the rTSD index is based on the thicknesses of various layers of the patient's retina that are connected to the left optic radiation and the right optic radiation of the patient. In some implementations, the sign of the rTSD index indicates whether the cause of the rTSD (e.g., a paramagnetic rim lesion, a central vein sign lesion, or another lesion) is located in the left hemisphere of the patient's brain (e.g., the left optic radiation) or the right hemisphere of the patient's brain (e.g., the right optic radiation). In some implementations, the absolute value of the rTSD index indicates the magnitude of the rTSD in one hemisphere of the patient's brain relative to the other hemisphere of the patient's brain. The above summary is not intended to represent each implementation or every aspect of the present disclosure. Additional features and benefits of the present disclosure are apparent from the detailed description and figures set forth below. BRIEF DESCRIPTION OF THE DRAWINGS The disclosure, and its advantages and drawings, will be better understood from the following description of representative embodiments together with reference to the accompanying drawings. These drawings depict only re