Encephalopathy Connectomic Collapse Atlas (ECCA-HYP) | Hypoxic–Ischemic Encephalopathy Biomarker Panel

SCF-ECCA-HYP-BIO-0007

Hypoxic–Ischemic Encephalopathy Biomarker Panel

Cerebral Hypoxia Connectomic Collapse Validation System

FDA-Aligned Endpoint Framework for Precision Acupuncture Planning

Encephalopathy Connectomic Collapse Atlas (ECCA-HYP)

I. PURPOSE

The SCF Hypoxic–Ischemic Encephalopathy (HIE) Biomarker Panel is designed to:

Establish hypoxic–ischemic encephalopathy diagnostic support
Quantify cerebral oxygen-deprivation injury severity
Measure neurovascular and connectomic collapse
Predict neurologic recovery versus deterioration
Stratify precision acupuncture neurocircuit selection
Monitor acute-to-chronic recovery transitions
Support FDA-aligned translational endpoint development
Enable precision forecasting of long-term neurofunctional outcomes

II. SCF HYPOXIC–ISCHEMIC ENCEPHALOPATHY BIOMARKER DOMAINS

Domain	Function
Oxygenation Status	Measures systemic hypoxic burden
Ischemic Injury	Measures cerebral ischemic damage
Neuroaxonal Injury	Measures neuronal destruction
Glial Activation	Measures astrocytic response
BBB Integrity	Measures neurovascular disruption
Neuroimmune Activation	Measures secondary inflammatory injury
Mitochondrial Function	Measures ATP-redox collapse
Autonomic Function	Measures brainstem-autonomic stability
Connectomic Function	Measures network synchronization
Sensorimotor Function	Measures motor network integrity
Cognitive Function	Measures cortical recovery
Outcome Prediction	Forecasts neurologic prognosis

III. OXYGENATION STATUS PANEL

Tier 1 Hypoxic Burden Layer

Biomarker	FDA-Aligned Assay	Normal	Mild Risk	Moderate Risk	Severe Risk
Arterial PaO₂	Blood Gas	>80 mmHg	60–80	40–60	<40
Oxygen Saturation (SpO₂)	Pulse Oximetry	>95%	90–95%	80–89%	<80%
Arterial Lactate	Clinical Chemistry	<2 mmol/L	2–3	3–5	>5
Mixed Venous O₂ Saturation	Blood Gas	>70%	60–70%	50–60%	<50%
Base Deficit	Blood Gas	0 to -2	-2 to -5	-5 to -10	<-10

Endpoint

Hypoxic Burden Index (HBI)

IV. ISCHEMIC INJURY PANEL

Tier 2 Cerebral Ischemia Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Ischemia Modified Albumin	Immunoassay	Normal	Elevated	High	Very High
HIF-1α	ELISA	Reference	Elevated	High	Very High
VEGF	ELISA	Normal	Elevated	High	Very High
Erythropoietin	Immunoassay	Reference	Elevated	High	Very High
LDH	Clinical Chemistry	Normal	Elevated	High	Very High

Endpoint

Ischemic Injury Severity Score (IISS)

V. NEUROAXONAL INJURY PANEL

Tier 3 Connectomic Injury Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
NfL	Simoa	<10 pg/mL	10–20	20–50	>50
Total Tau	Simoa	<2 pg/mL	2–4	4–8	>8
UCH-L1	ELISA	<100 pg/mL	100–200	200–400	>400
NSE	CLIA	<12 ng/mL	12–18	18–25	>25

Endpoint

Neuroaxonal Injury Index (NAII)

VI. GLIAL ACTIVATION PANEL

Tier 4 Astroglial Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
GFAP	Simoa	<120 pg/mL	120–250	250–500	>500
S100B	Immunoassay	<0.1 ng/mL	0.1–0.2	0.2–0.5	>0.5
YKL-40	ELISA	<60 ng/mL	60–100	100–150	>150
sTREM2	ELISA	Normal	Elevated	High	Very High

Endpoint

Glial Activation Severity Score (GASS)

VII. BBB INTEGRITY PANEL

Tier 5 Neurovascular Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Albumin Quotient	CSF/Serum	<6.5	6.5–8	8–12	>12
S100B	Immunoassay	<0.1	0.1–0.2	0.2–0.5	>0.5
MMP-9	ELISA	<150 ng/mL	150–250	250–400	>400
VEGF	ELISA	Normal	Elevated	High	Very High

Endpoint

BBB Permeability Index (BBPI)

VIII. NEUROIMMUNE ACTIVATION PANEL

Tier 6 Secondary Injury Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
IL-6	Multiplex	<2 pg/mL	2–10	10–50	>50
TNF-α	Multiplex	<5 pg/mL	5–15	15–30	>30
IL-1β	Multiplex	<1 pg/mL	1–5	5–15	>15
HMGB1	ELISA	Normal	Elevated	High	Very High
hsCRP	Immunoassay	<1 mg/L	1–3	3–10	>10

Endpoint

Secondary Injury Amplification Score (SIAS)

IX. MITOCHONDRIAL FAILURE PANEL

Tier 7 Bioenergetic Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
Lactate	Clinical Chemistry	0.5–2.0 mmol/L	2–3	3–5	>5
Pyruvate	LC-MS/MS	Normal	Elevated	High	Very High
Lactate/Pyruvate Ratio	LC-MS/MS	<20	20–30	30–40	>40
ATP Production Rate	Seahorse	Normal	↓10%	↓25%	↓50%
Mitochondrial DNA (cf-mtDNA)	qPCR	Low	Elevated	High	Very High

Endpoint

Bioenergetic Failure Index (BFI)

X. AUTONOMIC FAILURE PANEL

Tier 8 Brainstem-Autonomic Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
HRV SDNN	ECG	>100 ms	80–100	50–80	<50
RMSSD	ECG	>30 ms	20–30	10–20	<10
LF/HF Ratio	HRV	1–2	2–3	3–5	>5
Baroreflex Sensitivity	Autonomic Testing	Normal	Mild Reduction	Moderate Reduction	Severe Reduction

Endpoint

Autonomic Collapse Index (ACI)

XI. CONNECTOMIC FUNCTION PANEL

Tier 9 Connectomic Collapse Layer

Biomarker	Assay	Baseline	Mild	Moderate	Severe
EEG Delta Power	qEEG	Normal	+20%	+50%	+100%
EEG Theta Excess	qEEG	Normal	Mild	Moderate	Severe
Alpha Connectivity	qEEG	Normal	↓10%	↓25%	↓50%
rs-fMRI Connectivity	MRI	↓10%	↓25%	↓50%	↓75%
DTI Fractional Anisotropy	MRI-DTI	Normal	↓5%	↓10%	↓20%

Endpoint

Connectomic Collapse Index (CCI)

XII. SENSORIMOTOR FUNCTION PANEL

Tier 10 Motor Recovery Layer

Endpoint	Normal	Mild	Moderate	Severe
NIH Stroke Scale	0	1–4	5–15	>15
Modified Rankin Scale	0	1–2	3–4	5–6
Fugl-Meyer Motor Score	>95	75–95	40–74	<40
Gait Velocity	Normal	Mild Reduction	Moderate Reduction	Severe Reduction

Endpoint

Sensorimotor Recovery Index (SRI)

XIII. COGNITIVE ENDPOINT PANEL

Tier 11 Functional Outcome Layer

Endpoint	Normal	Mild	Moderate	Severe
MoCA	≥26	22–25	16–21	<16
Trail Making Test-B	<75 sec	75–120	120–180	>180
Digit Symbol Substitution	>90	75–90	50–75	<50
Glasgow Outcome Scale	Good Recovery	Moderate Disability	Severe Disability	Vegetative/Death

Endpoint

Hypoxic Connectomic Performance Score (HCPS)

XIV. SCF ACUPUNCTURE RESPONSE FORECAST PANEL

Biomarker Pattern	Predicted Dysfunction	Primary Acupuncture Network
Elevated Lactate + Low PaO₂	Hypoxic bioenergetic collapse	KI3 + ST36 + SP6
Elevated GFAP + S100B	Astroglial injury	GV20 + Sishencong + ST36
Elevated NfL + Tau	Neuroaxonal injury	GV20 + GV24 + GB20
Elevated IL-6 + HMGB1	Secondary neuroinflammatory injury	ST36 + LI11 + LI4
Reduced EEG Connectivity	Connectomic collapse	GV20 + GV24 + Sishencong
HRV suppression	Brainstem-autonomic dysfunction	PC6 + HT7 + CV17
Impaired motor scores	Sensorimotor network disruption	GB34 + BL40 + ST36
Elevated VEGF + BBB markers	Neurovascular instability	GV20 + PC6 + GB20

XV. SCF PRECISION FORECASTING MODEL

Low-Risk Recovery

Criteria:

Lactate <2 mmol/L
GFAP <250 pg/mL
NfL <20 pg/mL
MoCA >24
Preserved HRV

Predicted Response:

High likelihood of neurologic recovery and favorable neuromodulation responsiveness.

Intermediate Risk

Criteria:

Lactate 2–4 mmol/L
GFAP 250–500 pg/mL
Moderate EEG slowing
MoCA 18–24

Predicted Response:

Partial recovery requiring prolonged rehabilitation and neuromodulation support.

High-Risk Progression

Criteria:

Lactate >4 mmol/L
GFAP >500 pg/mL
NfL >50 pg/mL
Severe EEG slowing
MoCA <18
Significant DTI disruption

Predicted Response:

High risk of permanent neurologic injury and poor functional outcome.

XVI. COMPOSITE SCF HYPOXIC–ISCHEMIC ENCEPHALOPATHY SCORE (SCF-HIES)

Domain	Weight
Oxygenation Status	15%
Ischemic Injury	15%
Neuroaxonal Injury	15%
Glial Activation	10%
BBB Integrity	10%
Neuroimmune Activation	10%
Mitochondrial Function	10%
Connectomics	10%
Autonomics	3%
Sensorimotor Function	1%
Cognition	1%

Interpretation

Score	Classification
<20	Stable
20–40	Mild Hypoxic Connectomic Dysfunction
40–60	Moderate Collapse
60–80	Severe Hypoxic–Ischemic Encephalopathy
>80	Critical Cerebral Oxygen Failure

XVII. PRIMARY FDA-ALIGNED CLINICAL ENDPOINTS

Diagnostic-Support Endpoints

Arterial blood gas
Lactate
MRI-DWI/DTI
EEG
Neurologic examination

Predictive Endpoints

NfL
GFAP
Lactate/Pyruvate Ratio
HRV
DTI Fractional Anisotropy

Therapeutic Response Endpoints

Improvement in oxygenation metrics
Reduction in GFAP/NfL
Improvement in EEG connectivity
Improved HRV
Improved cognitive and motor outcomes

NEXT PANEL IN SEQUENCE

SCF-ECCA-TRA-BIO-0008

Traumatic Encephalopathy Biomarker Panel

(Neurotraumatic Connectomic Collapse Validation System)

MASTER REGISTRY INDEX

SCF-ECCA-HYP-BIO-0007 — Hypoxic–Ischemic Encephalopathy Biomarker Panel
SCF-ECCA-HYP-ACU-0007 — Hypoxic–Ischemic Encephalopathy Acupoint Neuro-Circuit Mapping Atlas
SCF-ECCA-0001 — Encephalopathy Connectomic Collapse Atlas
SCF-BIOMARKER-ENDPOINTS-0001 — SCF Biomarker Endpoint Validation Framework
SCF-PATH-PROT-0001 — SCF Pathophysiology Protocol
SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema