IP Library › Granted Patent US 12,431,243
Granted Patent B2
US 12,431,243 · App. 16/758,775 · Granted Sep 30, 2025

Medical system for diagnosing cognitive disease pathology and/or outcome

Inventors: Rabia Ahmad (Amersham, GB); Emmanuel Fuentes (Waukesha, WI); Quang Trung Nguyen (Vélizy-villacoublay, FR); Christopher Buckley (Amersham, GB); Jan Wolber (Amersham, GB)
Assignee: GE HEALTHCARE LIMITED
G16H50/20G16H50/50G16H50/70
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Quick Facts
Patent No.
US 12,431,243
App. No.
16/758,775
Granted
Sep 30, 2025
Kind
B2
Abstract

A medical system useful in the determination of future disease progression in a subject. More specifically the present invention applies machine learning techniques to aid prediction of disease pathology and clinical outcomes in subjects presenting with symptoms of cognitive decline and to expedite clinical development of novel therapeutics.

Claims (35)

1. An apparatus comprising:

memory storing instructions; and

a processor to execute the instructions to implement:

a first trained learning machine trained on first clinical data related to patient cognitive status to predict a brain disease pathology associated with a brain disease in a first set of subjects, the brain disease pathology including amyloid beta (AB) positivity in the brain, the first trained learning machine tuned for a clinical protocol to identify a second set of subjects from the first set of subjects, the second set of subjects having a first probability of the brain disease pathology greater than a first threshold; and

a second trained learning machine trained using a training data set created using image data and non-image data and deployed to predict a second probability of the brain disease pathology in the second set of subjects based on i) second clinical data related to patient cognitive status and ii) image-related data correlated with the second clinical data, the second trained learning machine tuned for the clinical protocol to select a third set of subjects from the second set of subjects, the third set of subjects having the second probability of the brain disease greater than a second threshold; and

a network interface to generate an output to trigger execution of the clinical protocol for the third set of subjects by arranging a computer system to display an indication and include the third set of subjects classified as a cohort for treatment, the treatment including administering a disease modifying drug (DMD) for the brain disease to the cohort via the clinical protocol, the brain disease including at least one of mild cognitive impairment (MCI) or Alzheimer's disease (AD).

2. The apparatus of claim 1 , wherein the clinical protocol is associated with a clinical trial for a drug.

3. The apparatus of claim 1 , wherein the clinical protocol is associated with a treatment plan for a patient.

4. The apparatus of claim 1 , wherein the image-related data includes at least one of a positron emission tomography (PET) image or a magnetic resonance (MR) image.

5. The apparatus of claim 1 , wherein the image-related data includes data related to quantified regions of at least one of a PET image or an MR image.

6. The apparatus of claim 1 , wherein the image-related data is first image-related data, and wherein the first trained learning machine further predicts the brain disease pathology using the first clinical data and second image-related data.

7. The apparatus of claim 1 , wherein the brain disease pathology is loss of dopamine-producing brain cells.

8. The apparatus of claim 1 , wherein at least one of the first clinical data or the second clinical data includes demographic data.

9. The apparatus of claim 1 , wherein the first trained learning machine includes at least a first machine-learned model, and wherein the second trained learning machine includes at least a second machine-learned model.

10. The apparatus of claim 9 , wherein at least one of the first machine-learned model or the second machine-learned model is rebuilt based on at least one of: i) a change in the respective first threshold or second threshold, ii) additional data related to at least one of the first clinical data or the second clinical data.

11. The apparatus of claim 10 , wherein at least one of the first machine-learned model or the second machine-learned model includes a plurality of folds, and wherein each of the plurality of folds is rebuilt to form a final model.

12. A non-transitory machine-readable medium including instructions that, when executed, cause a processor to at least:

process, using a first trained learning machine, a first set of subjects to identify a second set of subjects from the first set of subjects, the second set of subjects having a first probability of a brain disease pathology greater than a first threshold, the brain disease pathology including amyloid beta (AB) positivity in the brain, wherein the first trained learning machine is tuned for a clinical protocol and trained on first clinical data related to patient cognitive status to predict the brain disease pathology associated with a brain disease;

generate, using a second trained learning machine, a third set of subjects from the second set of subjects, the third set of subjects having a second probability of the brain disease pathology greater than a second threshold, wherein the second trained learning machine is tuned for the clinical protocol and trained using a training data set created using image data correlated with non-image data and deployed to predict the second probability of the brain disease in the second set of subjects based on i) second clinical data related to patient cognitive status and ii) image-related data; and

generate an output to trigger execution of the clinical protocol for the third set of subjects by arranging a computer system to display an indication and include the third set of subjects classified as a cohort for treatment, the treatment including administering a disease modifying drug (DMD) for the brain disease to the cohort via the clinical protocol, the brain disease including at least one of mild cognitive impairment (MCI) or Alzheimer's disease (AD).

13. The machine-readable medium of claim 12 , wherein the instructions, when executed, cause the processor to assess at least one of the first set of subjects or the second set of subjects with cognitive testing.

14. The machine-readable medium of claim 12 , wherein the instructions, when executed, cause the processor to obtain the image-related data from the second set of subjects.

15. The machine-readable medium of claim 12 , wherein the instructions, when executed, cause the processor to quantify regions in the image-related data.

16. The machine-readable medium of claim 12 , wherein the instructions, when executed, cause the processor to trigger patient treatment involving the clinical protocol.

17. The machine-readable medium of claim 12 , wherein the instructions, when executed, cause the processor to support a clinical trial using the clinical protocol.

18. The machine-readable medium of claim 12 , wherein the first trained learning machine includes at least a first machine-learned model and the second trained learning machine includes at least a second machine-learned model, and wherein the instructions, when executed, cause the processor to rebuild at least one of the first machine-learned model or the second machine-learned model based on at least one of: i) a change in the respective first threshold or second threshold, ii) additional data related to at least one of the first clinical data or the second clinical data.

19. An apparatus comprising:

memory storing instructions; and

a processor to execute the instructions to implement:

a first trained learning machine trained on first clinical data related to patient cognitive status to predict a brain disease pathology associated with a brain disease, the first set of subjects having a first probability of the brain disease pathology greater than a first threshold, the brain disease pathology including amyloid beta (AB) positivity in the brain; and

a second trained learning machine trained using a training data set created using image data and non-image data and deployed to predict a second probability of the brain disease pathology based on i) second clinical data related to patient cognitive status and ii) image-related data, the second set of subjects having the second probability of the brain disease greater than a second threshold,

the processor to form a third set of subjects based on at least one of the first set of subjects or the second set of subjects; and

a network interface to generate an output to trigger execution of a clinical protocol with the third set of subjects by arranging a computer system to display an indication and include the third set of subjects in the clinical protocol, the clinical protocol including treatment including administering a disease modifying drug (DMD) for the brain disease to the third set of subjects via the clinical protocol, the brain disease including at least one of mild cognitive impairment (MCI) or Alzheimer's disease (AD).

20. The apparatus of claim 1 , wherein the brain disease pathology is predicted using a radioactive diagnostic agent.

21. The apparatus of claim 20 , wherein the radioactive diagnostic agent includes at least one of Vizamyl™, Neuraceq™, or Amyvid™.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 23, 2021
From: AHMAD, RABIA; FUENTES, EMMANUEL; NGUYEN, QUANG TRUNG; BUCKLEY, CHRISTOPHER; WOLBER, JAN
To: GE HEALTHCARE LIMITED
Reel/Frame 056631/0693 →
Continuity (2)
Provisional Application 62579630 · Oct 31, 2017
Related Publication 20200258629A1 · Aug 13, 2020
References Cited (57)
US 8815508B2 · Roses · 2014 [cited by examiner]
US 9492114B2 · Reiman · 2016 [cited by examiner]
US 9687199B2 · Ithapu et al. · 2017 [cited by applicant]
US 9779213B2 · Donovan · 2017 [cited by examiner]
US 9788784B2 · Reiman · 2017 [cited by examiner]
US 11101039B2 · Albright · 2021 [cited by examiner]
US 20010034023A1 · Stanton, Jr. · 2001 [cited by examiner]
US 20020143563A1 · Hufford · 2002 [cited by examiner]
US 20020143577A1 · Shiffman · 2002 [cited by examiner]
US 20050283054A1 · Reiman · 2005 [cited by applicant]
US 20060099624A1 · Wang et al. · 2006 [cited by applicant]
US 20060184493A1 · Shiffman · 2006 [cited by examiner]
US 20090263507A1 · Roy · 2009 [cited by examiner]
US 20120184584A1 · Roses · 2012 [cited by examiner]
US 20130006671A1 · Hufford · 2013 [cited by examiner]
US 20140107494A1 · Kato et al. · 2014 [cited by applicant]
US 20140222444A1 · Cerello · 2014 [cited by examiner]
US 20160361385A1 · Tuszynski · 2016 [cited by examiner]
US 20170219611A1 · Ward et al. · 2017 [cited by applicant]
US 20170340262A1 · Momose et al. · 2017 [cited by applicant]
US 20180190369A1 · Wolz · 2018 [cited by examiner]
CN 1753675A · 2006 [cited by applicant]
CN 103493054A · 2014 [cited by applicant]
CN 103501783A · 2014 [cited by applicant]
CN 104611421A · 2015 [cited by applicant]
CN 105164536A · 2015 [cited by applicant]
JP 2016106940A · 2016 [cited by applicant]
JP 5959016B2 · 2016 [cited by applicant]
JP 2017192425A · 2017 [cited by applicant]
C. Ramirez, Jaime, et al., “Network-based biomarkers in Alzheimer's disease: review and future directions”, Frontiers in Aging Neuroscience, Feb. 2014, Vo. 6, Article 12, pp. 1-9, (Year: 2014). [cited by examiner]
International Search Report corresponding to International Application No. PCT/EP2018/079905, dated Oct. 31, 2018. [cited by applicant]
Pereira, Telma, et al., “Predicting progression of mild cognitive impairment to dementia using neuropsychological data: a supervised learing approach using time windows”, BMC Medical Informations and Decision Making, vo… [cited by applicant]
Casanova, Ramon, et al., “Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals”, Alzheimer's & Dementia: The Journal of the Alzheimer's Association, Els… [cited by applicant]
Babu, G. Sateesh, et al., “Parkinson's disease prediction using gene expression—A projection based learning meta-cognitive neural classifier approach”, Expert Systems with Applications, vol. 40, No. 5, Apr. 1, 2013, pp.… [cited by applicant]
Thurfjell et al., “Automated Quantification of 18F-Flutemetamol PET Activity for Categorizing Scans as Negative of Positive for Brain Amyloid: Concordance with Visual Image Reads,” Journal of Nuclear Medicine, 55, 2014,… [cited by applicant]
Korean Intellectual Property Office, “Notice of Preliminary Rejection,” issued in connection with Korean Patent Application No. 20207012136, dated Apr. 3, 2024, 18 pages. [English Translation Included]. [cited by applicant]
European Patent Office, “Partial European Search Report,” issued in connection with European Patent Application No. 24184555.1, dated Oct. 14, 2024, 18 pages. [cited by applicant]
Teipel et al., “The Relative Importance of Imaging Markers for the Prediction of Alzheimer's Disease Dementia in Mild Cognitive Impairment—Beyond Classical Regression,” Neurolmage: Clinical 8, May 21, 2015, 11 pages. [cited by applicant]
Korolev et al., “Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification,” Plos One, Feb. 22, 2016, 25 pages. [cited by applicant]
Tong et al., “A Novel Grading Biomarker for the Prediction of Conversion From Mild Cognitive Impairment to Alzheimer's Disease,” IEEE Transactions on Biomedical Engineering, vol. 64, No. 1, Jan. 2017, 11 pages. [cited by applicant]
Pereira et al., “Predicting Progression of Mild Cognitive Impairment to Dementia using Neuropsychological Data: A Supervised Learning Approach Using Time Windows,” BMC Medical Informatics and Decision Making, Jul. 19, 2… [cited by applicant]
Anand et al., “Amyloid Imaging: Poised for Integration into Medical Practice,” Neurotherapeutics, American Society for Experimental Neuro Therapeutics Inc, Aug. 29, 2016, 8 pages. [cited by applicant]
Rathore et al., “A Review on Neuroimaging-Based Classification Studies and Associated Feature Extraction Methods for Alzheimer's Disease and its Prodromal Stages,” Neurolmage 155, Elsevier, 2017, 19 pages. [cited by applicant]
Weiner et al., “Recent Publications From the Alzheimer's Disease Neuroimaging Initiative: Reviewing Progress Toward Improved AD Clinical Trials,” Alzheimers Dement, Mar. 22, 2017, 164 pages. [cited by applicant]
European Patent Office, “Extended European Search Report,” issued in connection with European Patent Application No. 24184555.1, dated Jan. 13, 2025, 16 pages. [cited by applicant]
Weiner et al., “Recent Publications from the Alzheimer's Disease Neuroimaging Initiative: Reviewing Progress Toward Improved AD Clinical Trials,” Alzheimer's and Dementia, Elsevier, vol. 13, No. 4, Mar. 22, 2017, 228 pa… [cited by applicant]
China National Intellectual Property Administration, “Search Report,” issued in connection with Chinese Patent Application No. 201880070412.9, dated Jul. 25, 2023, 3 pages. [English Translation]. [cited by applicant]
China National Intellectual Property Administration, “First Office Action,” issued in connection with Chinese Patent Application No. 201880070412.9, dated Jul. 28, 2023, 33 pages. [English Translation Included]. [cited by applicant]
Pereira et al., “Predicting Progression of Mild Cognitive Impairment to Dementia Using Neuropsychological Data: A Supervised Learning Approach Using Time Windows,” BMC Medical Informatics and Decision Making, vol. 17, N… [cited by applicant]
Dong et al., “Research Progress on 18F-FDG PET Imaging in Mild Cognitive Impairment,” Chinese Journal of Clinical Neuroscience, No. 2, Jun. 20, 2005, 10 pages. [English Translation Included]. [cited by applicant]
Cheng et al., “Research Advances on the Pathogenesis and Treatment of Alzheimer's Disease,” Journal of Zunyi Medical College, No. 6, Dec. 6, 2013, 8 pages. [English Translation Included]. [cited by applicant]
European Patent Office, “Communication Pursuant to Article 94(3) EPC,” issued in connection with European Patent Application No. 18799476.9, dated Mar. 28, 2023, 5 pages. [cited by applicant]
Japan Patent Office, “Search Report by Registered Search Organization,” issued in connection with Japanese Patent Application No. 2020-523752, dated Nov. 8, 2022, 70 pages. [English Translation Included]. [cited by applicant]
Japan Patent Office, “Notice of Reasons for Refusal,” issued in connection with Japanese Patent Application No. 2020-523752, dated Nov. 17, 2022, 8 pages. [English Translation Included]. [cited by applicant]
Japan Patent Office, “Written Opinion,” issued in connection with Japanese Patent Application No. 2020-523752, dated May 18, 2023, 11 pages. [English Translation Included]. [cited by applicant]
Japan Patent Office, Notice of Reasons for Refusal, issued in connection with Japanese Patent Application No. 2020-523752, dated Jul. 31, 2023, 10 pages. [English Translation Included]. [cited by applicant]
International Searching Authority, “International Preliminary Report on Patentability,” issued in connection with International Patent Application No. PCT/EP2018/079905, issued on May 5, 2020, 16 pages. [cited by applicant]
Cited By (1)
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