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US-20260123877-A1 - Transmission Device

US20260123877A1US 20260123877 A1US20260123877 A1US 20260123877A1US-20260123877-A1

Abstract

A method of diagnosing a neurodegenerative disorder (ND) in a patient comprising: (a) obtaining MRI image(s) of the patient's brain, (b) using the MRI image(s) of the patient's brain to segment sub-cortical structures associated with the ND into sub-regions, based on structural connectivity to cortical sub-regions, (c) extracting one or more MRI features from each of the sub-regions generated by the segmentation, and (d) using one or more machine learning techniques to classify the patient as being ND positive or ND negative based on comparisons of the one or more MRI features to at least one training data set that includes MRI features of each of the sub-regions generated by the segmentation of known ND positive controls and MRI features of each of the sub-regions generated by the segmentation of ND negative controls, thereby diagnosing ND. Also computer-based or cloud-based systems to diagnose a ND in a subject.

Inventors

  • Andreas Froese

Assignees

  • Andreas Froese

Dates

Publication Date
20260507
Application Date
20230925
Priority Date
20221124

Claims (20)

  1. 1 . A transmission device comprising: (i) a support frame; (ii) a driven wheel supported for rotation relative to the support frame; (iii) a drive wheel supported for rotation relative to the support frame such that a peripheral boundary of the drive wheel is in proximity to an engaged portion of the driven wheel, the drive wheel being configured to receive an input rotation, and the drive wheel being operatively connected to the driven wheel to transfer a rotation of the drive wheel in a first direction to a rotation of the driven wheel in a corresponding direction whereby a nip point is defined by a convergence between the peripheral boundary of the drive wheel and the engaged portion of the driven wheel as the drive wheel and the driven wheel are rotated in said first direction and said corresponding direction respectively; (iv) a plurality of driven elements supported on the driven wheel at circumferentially spaced apart locations about the driven wheel, each driven element being supported for reciprocating movement between a first position in interference with the drive wheel at the nip point and a second position displaced radially of the driven wheel relative to the first position whereby each driven element is arranged to be driven from the first position to the second position as it passes through the nip point between the drive wheel and the driven wheel; (v) a transfer linkage operatively connected between the driven elements and the driven wheel so as to transfer the reciprocating movement of the driven elements to rotation of the driven wheel in said corresponding direction; and (vi) an output member driven by the transfer linkage to provide an output rotation.
  2. 2 . The device according to claim 1 wherein the drive wheel is supported above the driven wheel such that the engaged portion of the driven wheel is in proximity to a top of the driven wheel and the driven elements are driven radially inward of the driven wheel from the first position to the second position.
  3. 3 . The device according to claim 1 wherein the driven wheel is an annular body and wherein the drive wheel is supported within the annular body above a lower portion of the driven wheel such that the engaged portion of the driven wheel is an inner boundary of the annular body in proximity to the driven wheel and the driven elements are driven radially outward of the driven wheel from the first position to the second position.
  4. 4 . The device according to claim 1 wherein the driven elements are supported on the driven wheel for sliding movement along a linear axis between the first position and the second position.
  5. 5 . The device according to claim 4 wherein the linear axis of each driven element is oriented radially of the driven wheel.
  6. 6 . The device according to claim 1 wherein each driven element includes a head surface arranged to be engaged by the drive wheel at the nip point, the head surface extending in said corresponding direction of rotation of the driven wheel at a slope radially of the driven wheel.
  7. 7 . The device according to claim 1 wherein each driven element includes a head surface arranged to be engaged by the drive wheel at the nip point, each head surface being directly adjacent the head surface of each adjacent driven element in the circumferential direction.
  8. 8 . The device according to claim 1 wherein the drive wheel is supported on the support frame for floating movement relative to the support frame whereby weight of the drive wheel is primarily carried by the engaged portion of the driven wheel upon which the drive wheel is seated.
  9. 9 . The device according to claim 1 wherein the drive wheel is weighted so as to have a greater mass than the driven wheel.
  10. 10 . The device according to claim 1 wherein a portion of the drive wheel makes rolling contact with a portion of the driven wheel.
  11. 11 . The device according to claim 1 wherein the drive wheel includes a first gear formed thereon for rotation with the drive wheel, wherein the driven wheel includes a second gear formed thereon for rotation with the driven wheel, and wherein the first gear and the second gear are operatively connected to transfer rotation from the drive wheel to the driven wheel.
  12. 12 . The device according to claim 1 further comprising a starter motor operatively connected to the drive wheel so as to provide the input rotation to the drive wheel.
  13. 13 . The device according to claim 12 further comprising a reduction drive connecting the starter motor to the drive wheel such that the drive wheel is driven at a slower speed than an output speed of the starter motor.
  14. 14 . The device according to claim 1 wherein the transfer linkage comprises: a biasing element associated with each driven element in which the biasing element biases the associated driven element to return from the second position to the first position after passing through the nip point between the drive wheel and the driven wheel; a driven gear associated with each driven element in which the driven gear is rotatably supported on the driven wheel; a one-way drive arrangement associated with each driven element in which the one-way drive arrangement operatively connects the associated driven element to the associated driven gear so as to (a) drive the driven gear in a drive direction when the driven element is displaced from the first position to the second position, and (b) allow the driven gear to continue to rotate in the drive direction when the driven element is returned from the second position to the first position; a transfer gear arranged to transfer drive from the driven gears in the drive direction to rotation of the driven wheel in said corresponding direction.
  15. 15 . The device according to claim 14 wherein the biasing element of each driven element comprises a biasing spring connected under compression between the driven element and a respective mounting surface on the driven wheel.
  16. 16 . The device according to claim 14 wherein each driven element is movable away from the second position beyond the first position to a respective overextended position, wherein the device further comprises a cushion spring associated with each driven element, and wherein each cushion spring is operatively connected to the associated driven element for biasing the associated driven element to the first position from the overextended position.
  17. 17 . The device according to claim 14 wherein the transfer gear comprises a ring gear mounted in fixed relation to the support frame whereby meshing engagement of the rotating driven gears with the ring transfer drives rotation of the driven wheel relative to the transfer gear on the support frame.
  18. 18 . The device according to claim 14 wherein the driven gear associated with each driven element comprises a first driven gear and a second driven gear connected for rotation together by a drive shaft and wherein the transfer gear comprises a first transfer gear operatively connected to the first driven gears and a second transfer gear operatively connected to the second driven gears.
  19. 19 . The device according to claim 14 wherein each one-way drive arrangement comprises: a row of gear teeth supported on the associated driven element; a spur gear rotatably supported on the driven wheel in meshing engagement with the row of gear teeth of the associated driven element; a drive shaft connecting the spur gear with the associated driven gear; and a one-way clutch transferring drive in only one direction of movement, the one-way clutch being operatively connected: (i) between the driven element and the row of gear teeth, (ii) between the spur gear and the drive shaft, or (iii) between the drive shaft and the driven gear.
  20. 20 . The device according to claim 1 wherein the transfer linkage comprises: a crankshaft assembly supported for rotation relative to the support frame, the crankshaft assembly comprising (i) a plurality of crankpins and (ii) a plurality of connecting rods coupling the crankpins to the driven elements respectively to drive rotation of the crankshaft assembly responsive to reciprocation of the driven elements; and at least one transfer gear driven to rotate by the crankshaft assembly, said at least one transfer gear being operatively connected to the driven wheel such that rotation of the crankshaft assembly drives rotation of the driven wheel relative to the support frame.

Description

FIELD OF TECHNOLOGY This disclosure relates to diagnostic, progression, and prognostic tests of neurodegenerative disorders using magnetic resonance imaging (MRI). More particularly, this disclosure relates to the identification of MRI biomarkers that allow for the diagnosis, staging, sub-typing and prognosis of neurodegenerative disorders using MRI, automated imaging analysis, and machine learning. BACKGROUND INFORMATION Neuronal loss and/or biochemical dysfunction in subregions of subcortical structures, such as the substantia nigra pars compacta (SNc) and the striatum, often underlie neurodegenerative diseases. For example, Parkinson's disease (PD) is a progressive neurodegenerative illness that is highly heterogeneous, with wide-ranging symptoms. PD patients manifest motor abnormalities such as rest tremor, slowed movements (i.e., bradykinesia) that are reduced in size and number (i.e., hypokinesia), and muscular rigidity.1,2 Currently, PD is diagnosed clinically when these cardinal motor symptoms appear, which arise due to degeneration of dopamine-producing neurons in the SNc and consequent dopamine restriction to subregions of the striatum. Dopamine-producing neurons in the ventral tegmental area (VTA), adjacent to the SNc and substantia nigra par reticulata (SNr), are only affected later in PD. Subcortical structures such as the SNc/VTA (substantia nigra pars compacta/ventral tegmental area) and the striatum, as well as the globus pallidus interna (GPi), globus pallidus externa (GPe), and the subthalamic nucleus (STN), are gray matter structures (i.e., clusters of neurons) located deep in the brain (FIG. 1). The SNc and VTA are adjacent subcortical structures, comprised of dopamine-producing neurons, that are not easily separated using standard approaches to imaging, though they are differentially affected by PD and are therefore important to measure separately. The striatum comprises the caudate nucleus, putamen, and nucleus accumbens (FIG. 1). The outer boundaries of subcortical structures, including the caudate nucleus and putamen, are easily discerned using neuroimaging such as MRI. However, subcortical structures lack internal margins to reliably delineate segments that are diverse in terms of function and vulnerability to diseases. This has limited the usefulness of neuroimaging to diagnose, track, and predict evolution of neurodegenerative disorders, which often involve abnormalities in subcortical structures. PD patients also experience a wide range of other motor and non-motor symptoms such as sleep and mood disorders, cognitive deficits, and autonomic dysfunction. Pathophysiology of these other motor and non-motor symptoms is more poorly understood. There is significant heterogeneity across PD patients in a) the intricate array of motor and non-motor symptoms that they experience, b) the stage of disease when symptoms appear, as well as c) the severity of symptoms and rates of progression of PD. Taken together, PD is a complex disorder, involving wide-ranging brain regions, that is difficult to diagnose and manage. There are currently no objective tests to diagnose PD in routine clinical practice (add reference here). PD is diagnosed through lengthy and complicated clinical assessments, ideally performed by neurologists with movement disorders expertise (i.e., the current diagnostic gold standard). Unfortunately, there are vastly insufficient numbers of movement disorder specialists. For example, there are approximately 80-100 movement disorder specialists practicing in Canada for a population of 38,781,291). In 2022, there were up to 90,000 people diagnosed with PD each year in North America, but there were as few as 88 movement disorders fellowship spots (i.e., specialist training opportunities) available each year in North America. Consequently, there were nearly 1,000 newly diagnosed PD patients alone for every newly-trained movement disorder neurologist. Movement disorder neurologists care not only for PD patients, but also for patients with other parkinsonian conditions and a diversity of other movement disorders. Currently, PD affects more than 3% of the population aged over 65. However, PD is the fastest-growing neurological disease in the world, due in part to its association with aging and ongoing demographic shifts and hence the gap between the availability of movement disorder specialists and PD patients will only increase. The 2011 prevalence of PD patients is predicted to double by 2031 in countries such as Canada. PD is a disabling disorder that has high economic costs. PD-related expenses exceed $50 billion annually at its current prevalence in the United States and significant expense is related to delayed diagnosis and introduction of symptomatic treatment. Diagnostic judgments and medication titration are optimally performed by movement disorder specialists, but more commonly are achieved by clinicians with lesser degrees of PD expertise. Diagnostic ambiguity is common in