BRAINAGE_END_TO_END_GUIDE.md

# BrainAge — Complete End-to-End Pipeline Guide

> **Purpose**: This document describes every step to reproduce the BrainAge
> brain-age prediction system from raw MRI scans to a deployed web
> application. Provide this file to any AI assistant or human collaborator
> and they can replicate the full workflow.

---

## Table of Contents

1. [Project Overview](#1-project-overview)
2. [Hardware & Software Prerequisites](#2-hardware--software-prerequisites)
3. [Repository Layout](#3-repository-layout)
4. [Dataset: The Golden Collection](#4-dataset-the-golden-collection)
5. [Phase 1 — Preprocessing (batch_preprocess)](#5-phase-1--preprocessing)
6. [Phase 2 — Cache Preparation (cache_prep)](#6-phase-2--cache-preparation)
7. [Phase 3 — Train/Val/Test Split (data_split)](#7-phase-3--trainvaltest-split)
8. [Phase 4 — Model Training (train)](#8-phase-4--model-training)
9. [Phase 5 — Evaluation (evaluate)](#9-phase-5--evaluation)
10. [Phase 6 — Post-Training Clinical Finalization (finalize)](#10-phase-6--post-training-finalization)
11. [Phase 7 — Single-Subject Inference (infer_age)](#11-phase-7--single-subject-inference)
12. [Phase 8 — 3D Viewer Demo (viewer)](#12-phase-8--3d-viewer-demo)
13. [Phase 9 — FastAPI Web Application (webapp)](#13-phase-9--fastapi-web-application)
14. [Phase 10 — Deployment](#14-phase-10--deployment)
15. [Troubleshooting](#15-troubleshooting)
16. [File Reference Table](#16-file-reference-table)

---

## 1. Project Overview

BrainAge predicts **brain age** from T1-weighted MRI scans using a dual-branch
deep learning model (3D SFCN + tabular MLP). A positive brain-age gap (BAG =
predicted − chronological) may indicate accelerated brain aging; a negative
BAG may suggest delayed maturation.

**Pipeline stages:**

```
Raw T1 NIfTI
  → skull-strip (HD-BET, GPU)
  → bias correction (N4, ANTs)
  → MNI registration (ANTs affine)
  → z-score normalization
  → segmentation (Harvard-Oxford atlas, 69 regions)
  → volumetric measurements (per-region mm³)
  → cache tensor (.pt: 128×144×112 volume + 86-dim tabular vector)
  → train BrainAgeDual model (SFCN 3D CNN + MLP, regression)
  → evaluate (MAE, per-age-bin, TTA)
  → post-training: ComBat harmonization, normative curves, QC
  → inference: predict brain age for new subjects
  → 3D viewer: interactive NiiVue + Three.js visualization
  → web app: FastAPI dashboard + chatbot + PDF reports
```

---

## 2. Hardware & Software Prerequisites

### Minimum hardware
| Component | Requirement |
|-----------|------------|
| GPU | NVIDIA GPU with ≥ 16 GB VRAM (tested on A10G 24 GB) |
| RAM | 16 GB (batch preprocess uses memory watchdog) |
| Disk | 200 GB free (raw ~55 GB + cache ~25 GB + outputs + scratch) |

### Software stack
```bash
# OS: Ubuntu 22.04+ (tested on 24.04)
# Python 3.12+

# Create virtual environment
python3.12 -m venv .venv
source .venv/bin/activate

# Core ML
pip install torch torchvision --index-url https://download.pytorch.org/whl/cu121
pip install monai nibabel nilearn antspyx scikit-image

# Brain extraction
pip install HD-BET  # provides `hd-bet` CLI

# Pipeline utilities
pip install pandas numpy psutil pynvml

# Web app (optional, for Phase 9+)
pip install fastapi uvicorn[standard] python-multipart jinja2 itsdangerous
pip install pydantic-settings sqlalchemy alembic
pip install "passlib[bcrypt]" "bcrypt>=4.0,<4.2"
pip install groq sentence-transformers faiss-cpu
pip install "weasyprint>=62,<63" markdown pypdf httpx

# All versions are pinned in webapp/requirements.txt
```

### Environment variables (`.env`)
```ini
GROQ_API_KEY=<your-groq-api-key>       # for chatbot + PDF narrative
GROQ_MODEL=openai/gpt-oss-120b
ANTHROPIC_API_KEY=<optional>            # for Claude-based clinical reports
SESSION_SECRET=<64-random-chars>        # for webapp sessions
```

---

## 3. Repository Layout

```
/home/MRI-DataSet/
├── Golden-0-to-25/          # Raw NIfTIs, 4782 subjects age 0–25
│   ├── manifest.csv         # subject_id, age, sex, dataset, file_path, …
│   └── DataSet-*_*/         # per-source-dataset folders with NIfTI files
├── Golden-25plus/           # Raw NIfTIs, 1370 subjects age 25–86
│   ├── manifest.csv
│   └── DataSet-*_*/
├── _train/                  # Training workspace (gitignored)
│   ├── cache/               # .pt tensors (one per subject)
│   ├── scratch/             # temporary preprocessing working dirs
│   ├── outputs/             # Tier-B clinical artifacts per subject
│   └── logs/                # preprocess_status.csv, master.log, err_*.log
├── _demo/
│   └── runs/                # 10 demo subjects with full outputs + meshes
├── pipeline_v2/             # All pipeline code
│   ├── preprocess.py        # skull-strip + N4 + MNI register + z-norm
│   ├── segment.py           # Harvard-Oxford atlas segmentation
│   ├── batch_preprocess.py  # Memory-safe parallel batch driver
│   ├── cache_prep.py        # Build .pt cache tensors
│   ├── data_split.py        # Stratified train/val/test split
│   ├── model.py             # BrainAgeDual (SFCN + tabular MLP)
│   ├── train.py             # Two-phase training with early stopping
│   ├── evaluate.py          # Test-set evaluation with TTA
│   ├── infer_age.py         # Single-subject inference (checkpoint-aware)
│   ├── anomaly.py           # Per-region z-score anomaly detection
│   ├── normative_fit.py     # Fit age-conditional region norms
│   ├── harmonize.py         # ComBat multi-site harmonization
│   ├── finalize.py          # Post-training orchestrator
│   ├── qc.py                # Automated quality control
│   ├── cognitive_rollup.py  # Map regions → cognitive domains
│   ├── pattern_detect.py    # Detect clinical patterns in region data
│   ├── llm_explain.py       # Generate clinical narrative (Claude/MedGemma)
│   ├── volume_age_prior.py  # Literature-based volume-to-age fallback
│   ├── backfill_outputs.py  # Reconstruct outputs from cache for old runs
│   ├── regen_reports.py     # Regenerate all report.md files
│   ├── run_pipeline.py      # Single-subject end-to-end orchestrator
│   ├── run_demo_10.py       # Quick 10-subject demo
│   ├── brainage_sfcn.pt     # ← trained checkpoint (created in Phase 4)
│   ├── norms.json           # ← normative curves (created in Phase 6)
│   ├── combat_params.json   # ← ComBat params (created in Phase 6)
│   ├── vol_age_prior.json   # Volume-to-age lookup table
│   ├── mni152_T1_1mm_brain.nii.gz
│   └── viewer/              # Standalone 3D viewer
│       ├── serve.py
│       ├── mesh_builder.py
│       └── static/          # index.html, viewer.html
└── webapp/                  # FastAPI web application
    ├── app/
    │   ├── main.py
    │   ├── config.py
    │   ├── db.py
    │   ├── security.py
    │   ├── deps.py
    │   ├── models/          # User, Patient, Scan, ChatMessage, AuditLog
    │   ├── routers/         # auth, index, dashboard, patients, viewer, …
    │   ├── services/        # groq_client, rag, stats, preprocess_sync, …
    │   ├── templates/       # Jinja2 HTML
    │   └── static/          # JS, CSS
    ├── alembic/
    ├── docs/                # RAG corpus (markdown)
    ├── data/                # DB, uploads, outputs, reports, rag_index
    ├── Dockerfile
    ├── docker-compose.yml
    ├── run_dev.sh
    └── requirements.txt
```

---

## 4. Dataset: The Golden Collection

### Manifests

Two CSV manifests define the full dataset:

| File | Subjects | Age range |
|------|----------|-----------|
| `Golden-0-to-25/manifest.csv` | 4,782 | 0 – 25 years |
| `Golden-25plus/manifest.csv` | 1,370 | 25 – 86 years |
| **Total** | **6,152** | **0 – 86 years** |

### Manifest columns
```
dataset, subject_id, split, age_years, age_label_type, chronological_age,
brain_age, sex, healthy, modality, notes, file_path, golden_path
```

### Source datasets (12 total)
| ID | Name | Age focus |
|----|------|-----------|
| DataSet-1 | BCP (Baby Connectome) | 0–5 y |
| DataSet-2 | Calgary Preschool | 2–7 y |
| DataSet-3 | ds002726 | 3–21 y |
| DataSet-4 | ds000248 | 30 y (single adult) |
| DataSet-5 | PTBP (Pediatric Template Brain) | 5–18 y |
| DataSet-6 | IXI | 20–86 y |
| DataSet-7 | MPI-Leipzig | 20–40 y |
| DataSet-8 | AOMIC-ID1000 | 18–33 y |
| DataSet-9 | NKI-Rockland | 6–85 y |
| DataSet-10 | ABIDE-I | 6–56 y |
| DataSet-11 | ABIDE-II | 5–60 y |
| DataSet-12 | ADHD-200 | 7–22 y |

### Hosted copies
- **Hugging Face**: `bilalahmad176176/BrainAge-Golden-Raw` (public)
- Each golden_path is a symlink/copy named `<subject_id>__<original>.nii.gz`

---

## 5. Phase 1 — Preprocessing

**Module**: `pipeline_v2/batch_preprocess.py`
**Input**: Raw T1w NIfTIs listed in manifest.csv
**Output**: Preprocessed files in `_train/scratch/proc_<sid>/` → cached to `_train/cache/<sid>.pt`

### What each step does

| Step | Tool | Time/subject | Output |
|------|------|-------------|--------|
| Skull-strip | HD-BET (GPU) | ~15-30 s | `brain.nii.gz`, `brain_bet.nii.gz` (mask) |
| Bias correction | N4 (ANTsPy) | ~10 s | `brain_n4.nii.gz` |
| MNI registration | ANTs Affine | ~30 s | `brain_mni.nii.gz`, `brain_mask_mni.nii.gz` |
| Z-score normalize | NumPy | <1 s | `brain_mni_znorm.nii.gz` |
| Segmentation | Harvard-Oxford atlas | ~2 s | `segmentation.nii.gz`, `measurements.csv` |
| Volume rescaling | — | — | Rescales MNI volumes back to native-space proportions |
| Anomaly scoring | `anomaly.py` | <1 s | `anomalies.csv` |
| Cache tensor | `cache_prep.py` | <1 s | `<sid>.pt` (volume fp16 + tab fp32 + age + meta) |

### Command

```bash
cd /home/MRI-DataSet
source .venv/bin/activate

python -m pipeline_v2.batch_preprocess \
    --manifests Golden-0-to-25/manifest.csv \
                Golden-25plus/manifest.csv \
    --cache_dir  _train/cache \
    --scratch_root _train/scratch \
    --logs_dir   _train/logs \
    --workers 2
```

### Memory safety

The batch driver has a built-in watchdog:
- **RAM throttle at 75 %**, panic SIGSTOP at 85 %
- **VRAM throttle at 80 %**, panic SIGSTOP at 90 %
- Workers are recycled every N subjects to prevent C-allocator memory creep
- `OMP_NUM_THREADS=2` per worker to prevent ANTs from spawning 16 threads

### Resumability

- If `cache/<sid>.pt` exists → **skipped** (idempotent)
- `preprocess_status.csv` is append-only, flushed after every subject
- Safe to SIGKILL and restart — picks up where it left off

### Monitoring

```bash
# Live progress
tail -f _train/logs/master.log

# Status counts
awk -F, 'NR>1{c[$5]++} END{for(k in c) print k,c[k]}' \
    _train/logs/preprocess_status.csv

# Cache count
ls _train/cache/*.pt | wc -l
```

### Expected runtime
- 6,152 subjects × ~85 s / 2 workers ≈ **72 hours** on A10G
- Expect ~1–2 % failures on first pass (mostly input quality issues)
- Retry with `--retry-failed` or just rerun (cache skips successes)

### Retry fix (built into preprocess.py)

`skull_strip()` has `retries=2` and verifies output file size.
`_ants_write_retry()` retries ITK NIfTI writes up to 3× with backoff.
These recover ~80 % of transient I/O failures.

---

## 6. Phase 2 — Cache Preparation

**Module**: `pipeline_v2/cache_prep.py`
**Note**: This is integrated INTO `batch_preprocess.py` — each worker calls
cache_prep at the end of its subject processing. No separate run needed.

### Cache tensor format (`<sid>.pt`)
```python
{
    "volume": torch.float16,   # shape (128, 144, 112) — resized from 182×218×182
    "tab":    torch.float32,   # shape (86,) — 70 region vols (log1p/12) + 3 sex + 13 site
    "age":    torch.float32,   # scalar — chronological age in years
    "meta":   dict,            # {subject_id, site, sex, age, split}
}
```

### Tabular vector breakdown (86 dimensions)
- Dims 0–69: log1p(volume_mm³) / 12 for each of the 70 Harvard-Oxford regions
- Dims 70–72: one-hot sex encoding [M, F, U]
- Dims 73–85: one-hot site encoding (13 datasets)

### Volume shape
Standard resize to `(128, 144, 112)` via trilinear interpolation.
Input: `brain_mni_znorm.nii.gz` (182×218×182 in MNI space).

---

## 7. Phase 3 — Train/Val/Test Split

**Module**: `pipeline_v2/data_split.py`
**Input**: Manifest CSV(s)
**Output**: `split.csv` with train/val/test assignments

```bash
python -m pipeline_v2.data_split \
    --manifests Golden-0-to-25/manifest.csv \
                Golden-25plus/manifest.csv \
    --out _train/split.csv
```

### Split strategy
- **Stratified by (site, age_bin)** — ensures every site × age combination
  is represented in all splits
- **Age bins**: 0–2, 2–5, 5–12, 12–18, 18–25, 25–50, 50–80
- **Ratios**: 75 % train / 10 % validation / 15 % test
- **Deterministic**: seed=42, reproducible

### Result (approximate)
| Split | Count |
|-------|-------|
| train | ~4,614 |
| val   | ~615 |
| test  | ~923 |

---

## 8. Phase 4 — Model Training

**Module**: `pipeline_v2/train.py`
**Architecture**: `pipeline_v2/model.py` — `BrainAgeDual`

### Model architecture: BrainAgeDual

```
Image branch (SFCN — Peng 2021):
  3D CNN: Conv3d(1→32→64→128→256→256→64) with BN + MaxPool + ReLU
  → AdaptiveAvgPool3d(1) → flatten → emb_dim=128

Tabular branch (MLP):
  Linear(86→128) → ReLU → Dropout(0.3) → Linear(128→128)

Fusion:
  concat(image_emb, tab_emb) → Linear(256→64) → ReLU → Dropout → Linear(64→1)

Total params: ~3M
Output: predicted age (scalar, years)
Loss: L1Loss (MAE)
```

### Training strategy

**Two-phase approach:**

#### Phase A — Lifespan pretraining
```bash
python -m pipeline_v2.train \
    --cache_dir _train/cache \
    --split_csv _train/split.csv \
    --out_ckpt  pipeline_v2/brainage_sfcn.pt \
    --epochs 60 \
    --batch 4 \
    --lr 3e-4
```

#### Phase B — Fine-tune on 0–25 subset (pediatric focus)
```bash
python -m pipeline_v2.train \
    --cache_dir _train/cache \
    --split_csv _train/split.csv \
    --resume_ckpt pipeline_v2/brainage_sfcn.pt \
    --age_max 25 \
    --epochs 30 \
    --lr 1e-4 \
    --out_ckpt pipeline_v2/brainage_sfcn.pt
```

### Training features
- **Mixed precision** (fp16) + gradient clipping
- **Linear warmup** (5 epochs) + **cosine LR decay**
- **Weighted sampler** for age-bin balance (prevents bias toward
  over-represented age groups)
- **MONAI augmentation**: random affine, random flip, intensity shift
- **Val-MAE early stopping** (patience=10)
- **CSV metrics log**: epoch, train_loss, val_loss, val_mae, lr

### Checkpoint format
```python
{
    "model": state_dict,
    "optimizer": optimizer_state,
    "epoch": int,
    "val_mae": float,
    "n_tabular": 86,
    "config": {...}
}
```

### Expected results (on this dataset)
| Metric | Expected range |
|--------|---------------|
| Overall MAE | 2.0 – 3.5 years |
| 0–2 y MAE | 1.0 – 2.0 years |
| 2–18 y MAE | 1.5 – 3.0 years |
| 18+ y MAE | 2.5 – 4.0 years |

---

## 9. Phase 5 — Evaluation

**Module**: `pipeline_v2/evaluate.py`

```bash
python -m pipeline_v2.evaluate \
    --cache_dir _train/cache \
    --split_csv _train/split.csv \
    --ckpt pipeline_v2/brainage_sfcn.pt \
    --out_csv _train/eval_results.csv \
    --tta 5
```

### What it computes
- Per-subject predictions with 5× flip TTA
- Overall MAE, median AE, R², correlation
- Per-age-bin MAE breakdown
- Per-site MAE breakdown
- Scatter plot data (true age vs predicted)

---

## 10. Phase 6 — Post-Training Finalization

**Module**: `pipeline_v2/finalize.py`

This orchestrator runs sequentially after training completes:

```bash
python -m pipeline_v2.finalize \
    --manifests Golden-0-to-25/manifest.csv \
                Golden-25plus/manifest.csv \
    --cache_dir _train/cache \
    --outputs_dir _train/outputs
```

### Stage 1: ComBat harmonization (`harmonize.py`)
- Removes scanner/site batch effects from per-region volumes
- Preserves biological variance (age, sex as covariates)
- Output: `pipeline_v2/combat_params.json`

### Stage 2: Normative curve fitting (`normative_fit.py`)
- Fits age-conditional mean and SD for each of 70 regions, stratified by sex
- Uses monotone cubic splines (similar to Bethlehem 2022 brain charts)
- Output: `pipeline_v2/norms.json`
- This replaces the synthetic `expected_region_volume()` baseline

### Stage 3: Rebuild anomaly tables
- Reruns `anomaly.py` on all subjects using fitted norms instead of crude σ
- z-scores become properly calibrated

### Stage 4: BAG confidence intervals
- Monte Carlo dropout on the trained model
- Adds confidence intervals to each subject's report

### Stage 5: QC re-check
- Volume sanity, z-norm range, registration quality
- Flags ~3–5 % for manual review

### Manual commands (if not using finalize.py)
```bash
# Harmonization alone
python -m pipeline_v2.harmonize \
    --cache _train/cache \
    --manifests Golden-0-to-25/manifest.csv Golden-25plus/manifest.csv \
    --out pipeline_v2/combat_params.json

# Normative fit alone
python -m pipeline_v2.normative_fit \
    --cache _train/cache \
    --manifests Golden-0-to-25/manifest.csv Golden-25plus/manifest.csv \
    --out pipeline_v2/norms.json

# Backfill outputs for subjects cached before outputs existed
python -m pipeline_v2.backfill_outputs \
    --cache_dir _train/cache \
    --outputs_dir _train/outputs
```

---

## 11. Phase 7 — Single-Subject Inference

**Module**: `pipeline_v2/infer_age.py`

### How it works
1. Checks for `pipeline_v2/brainage_sfcn.pt`
2. **If checkpoint exists**: loads BrainAgeDual, runs 5× flip-TTA inference
3. **If no checkpoint**: falls back to `volume_age_prior.py` (literature-based
   volume-to-age curve). The response includes `"predicted_source":
   "volume_prior_untrained"` as an honesty flag.

### Programmatic usage
```python
from pipeline_v2.infer_age import predict_age
result = predict_age(
    mni_znorm=Path("brain_mni_znorm.nii.gz"),
    meas_csv=Path("measurements.csv"),
    total_brain_mm3=1240000.0,
    sex="F",
    site="DataSet-6_IXI"
)
# result = {"predicted_brain_age": 32.5, "predicted_source": "sfcn_tta", ...}
```

### End-to-end single subject
```bash
python -m pipeline_v2.run_pipeline \
    /path/to/t1.nii.gz \
    sub-001 \
    25.0 \
    F \
    /tmp/output_sub001
```

---

## 12. Phase 8 — 3D Viewer Demo

**Module**: `pipeline_v2/viewer/serve.py`

```bash
# Start the standalone viewer
python -m uvicorn pipeline_v2.viewer.serve:app --host 0.0.0.0 --port 8765
# Open http://localhost:8765
```

### Features
- Subject list with age, predicted age, BAG
- NiiVue 2D slice views (axial/coronal/sagittal)
- Three.js 3D mesh rendering (marching cubes from segmentation)
- Per-region panel: volume, expected, deviation %, z-score, percentile
- Tissue composition (GM/WM/CSF ratios)
- Bilateral asymmetry index
- Lobe-wise abnormality summaries
- Cognitive domain rollup
- Clinical pattern detection
- Top findings bullets

### Demo data
10 subjects in `_demo/runs/` with full outputs including pre-built meshes.

### Hosted version
HF Space: `bilalahmad176176/BrainAge-3D-Viewer`

---

## 13. Phase 9 — FastAPI Web Application

**Location**: `webapp/`

### Architecture
- **Backend**: FastAPI + SQLAlchemy (SQLite) + Alembic migrations
- **Frontend**: Jinja2 templates + Tailwind CSS + vanilla JS + Chart.js
- **Auth**: Cookie-signed sessions, bcrypt passwords, admin + staff roles
- **LLM**: Groq `gpt-oss-120b` streaming via SSE
- **RAG**: FAISS + sentence-transformers/all-MiniLM-L6-v2 over project docs
- **PDF**: WeasyPrint HTML→PDF with Groq narrative + user signature

### Pages / features
| Route | Feature |
|-------|---------|
| `/` | Landing page + RAG chatbot (project Q&A) |
| `/login` | Authentication |
| `/dashboard` | KPIs, Chart.js graphs, activity heatmap, recent uploads |
| `/patients` | Patient list (CRUD) |
| `/patients/new` | Create patient |
| `/patients/{pid}/upload` | Upload MRI NIfTI → triggers full pipeline |
| `/scans/{id}/view` | 3D viewer + patient-scoped medical chatbot |
| `/scans/{id}/report` | Generate + download PDF clinical report |
| `/admin/users` | Admin user management |
| `/settings` | Signature upload for PDF reports |

### Quick start
```bash
cd webapp
cp .env.example .env  # fill SESSION_SECRET + GROQ_API_KEY
./run_dev.sh
# or
python -m uvicorn app.main:app --host 0.0.0.0 --port 8011 --reload
```

### Default credentials
| Username | Password | Role |
|----------|----------|------|
| `admin` | `admin` | admin |

**Change the admin password after first login.**

### Database models
- `User` (username, email, role, pwd_hash, signature_image_path)
- `Patient` (first_name, last_name, dob, sex, notes)
- `Scan` (patient_id, uploaded_at, status, predicted_age, bag, file_path)
- `ChatMessage` (scan_id, role, content, created_at)
- `AuditLog` (user_id, action, detail, created_at)

### How upload processing works
1. User uploads `.nii.gz` on `/patients/{pid}/upload`
2. Server validates NIfTI header, saves to `data/uploads/{pid}/`
3. Creates Scan row (status=processing)
4. Shows full-page spinner (`patients/processing.html`)
5. Blocking call to `preprocess_sync.run_pipeline_for_scan()`:
   - preprocess → segment → infer_age → score_regions
   - Copies all outputs (including NIfTIs!) to `data/outputs/{scan_id}/`
   - Updates Scan row with predicted_age, bag, status=completed
6. Redirects to 3D viewer

---

## 14. Phase 10 — Deployment

### Docker
```bash
cd webapp
cp .env.example .env   # edit SESSION_SECRET, GROQ_API_KEY
docker compose up -d --build
# browse http://localhost:8000
```

### Production checklist
1. Set a real `SESSION_SECRET` (64+ random chars)
2. Set `COOKIE_SECURE=1` behind HTTPS (nginx/Caddy reverse proxy)
3. Restrict `TRUSTED_HOSTS` to your real domain(s)
4. Change admin password after first login
5. Back up `data/webapp.db` and `data/outputs/` regularly
6. Run migrations on upgrade: `docker compose exec web alembic upgrade head`

### Hugging Face Spaces
A Docker-based Space is deployed at `bilalahmad176176/BrainAge-3D-Viewer`
(standalone viewer with 10 demo subjects, no auth).

---

## 15. Troubleshooting

### Preprocessing

| Problem | Cause | Fix |
|---------|-------|-----|
| `skull_strip: 16000+ s` | Running on CPU (no CUDA) | Ensure `nvidia-smi` works, torch sees GPU |
| `NiftiImageIO failed to write` | Transient I/O contention | Built-in `_ants_write_retry()` handles it; if persistent, check disk space |
| `brain_bet.nii.gz does not exist` | HD-BET silently failed | `skull_strip()` retries 2×; if persistent, the input NIfTI is likely corrupt |
| OOM during batch | Too many workers / too little RAM | Reduce `--workers 1`; watchdog will SIGSTOP at 85% RAM |

### Training

| Problem | Fix |
|---------|-----|
| CUDA OOM | Reduce `--batch 2` or `--batch 1` |
| Loss not decreasing | Check split.csv exists and has all subjects; verify cache integrity |
| Slow training | Ensure `.pt` cache is on SSD, not NFS |

### Webapp

| Problem | Fix |
|---------|-----|
| `unhashable type: 'dict'` | Starlette TemplateResponse signature changed — pass `request` as 1st arg |
| `password cannot be longer than 72 bytes` | Pin `bcrypt>=4.0,<4.2` for passlib compatibility |
| Viewer stuck on "loading…" | `brain_mni_znorm.nii.gz` missing from scan output dir — rerun preprocess or backfill |
| Port 8000 in use | Change port: `PORT=8011 ./run_dev.sh` |

---

## 16. File Reference Table

| File | Purpose | Created by |
|------|---------|-----------|
| `Golden-*/manifest.csv` | Dataset manifests with age, sex, paths | Manual curation |
| `_train/cache/<sid>.pt` | Preprocessed tensor cache | `batch_preprocess.py` |
| `_train/logs/preprocess_status.csv` | Per-subject status log | `batch_preprocess.py` |
| `_train/logs/master.log` | Driver log with progress/ETA | `batch_preprocess.py` |
| `_train/split.csv` | Train/val/test assignments | `data_split.py` |
| `pipeline_v2/brainage_sfcn.pt` | Trained model checkpoint | `train.py` |
| `pipeline_v2/norms.json` | Normative curves (per-region) | `normative_fit.py` |
| `pipeline_v2/combat_params.json` | ComBat harmonization params | `harmonize.py` |
| `pipeline_v2/vol_age_prior.json` | Volume-to-age fallback curve | `volume_age_prior.py` |
| `_train/outputs/<sid>/` | Tier-B clinical artifacts | `batch_preprocess.py` or `backfill_outputs.py` |
| `_demo/runs/<sid>/` | Demo subjects with full outputs + meshes | `run_demo_10.py` |
| `webapp/data/webapp.db` | SQLite database | FastAPI lifespan |
| `webapp/data/outputs/<scan_id>/` | Web upload scan outputs | `preprocess_sync.py` |
| `webapp/data/reports/<scan_id>/` | Generated PDF reports | `pdf_generator.py` |

---

## Quick-Start Cheat Sheet

```bash
# 1. Preprocess all 6,152 subjects (~72h)
python -m pipeline_v2.batch_preprocess \
    --manifests Golden-0-to-25/manifest.csv Golden-25plus/manifest.csv \
    --cache_dir _train/cache --scratch_root _train/scratch \
    --logs_dir _train/logs --workers 2

# 2. Generate train/val/test split
python -m pipeline_v2.data_split \
    --manifests Golden-0-to-25/manifest.csv Golden-25plus/manifest.csv \
    --out _train/split.csv

# 3. Train (lifespan → finetune)
python -m pipeline_v2.train \
    --cache_dir _train/cache --split_csv _train/split.csv \
    --out_ckpt pipeline_v2/brainage_sfcn.pt --epochs 60 --batch 4

python -m pipeline_v2.train \
    --cache_dir _train/cache --split_csv _train/split.csv \
    --resume_ckpt pipeline_v2/brainage_sfcn.pt \
    --age_max 25 --epochs 30 --lr 1e-4 \
    --out_ckpt pipeline_v2/brainage_sfcn.pt

# 4. Evaluate
python -m pipeline_v2.evaluate \
    --cache_dir _train/cache --split_csv _train/split.csv \
    --ckpt pipeline_v2/brainage_sfcn.pt --tta 5

# 5. Post-training finalization
python -m pipeline_v2.finalize \
    --manifests Golden-0-to-25/manifest.csv Golden-25plus/manifest.csv \
    --cache_dir _train/cache --outputs_dir _train/outputs

# 6. Launch webapp
cd webapp && ./run_dev.sh
```

---

*Last updated: 2026-04-24. Generated from the live BrainAge pipeline on
an NVIDIA A10G (24 GB VRAM) / 16 GB RAM / 193 GB disk Ubuntu server.*