Scripts/OM_reg_unpair.py

"""

OM_reg_unpair.py — Unpaired all-to-all registration using OMorpher.



Registers every subject to every other subject in a nested loop.

Output naming uses Tgt/Src prefixes instead of the Patient/Slice barcode.

Computes DSC, ASD, HD for organ labels (excludes tumour/lesion labels)

and saves per-pair tables and summary statistics as CSVs.



Usage:

    python Scripts/OM_reg_unpair.py -C Config/config_om.yaml

"""

import os
import sys

# Add project root to path so imports work from Scripts/
sys.path.insert(0, os.path.dirname(os.path.dirname(os.path.abspath(__file__))))

import csv
import numpy as np
import torch
import torch.nn.functional as F
import nibabel as nib
import yaml
import SimpleITK as sitk
from scipy.ndimage import distance_transform_edt, binary_erosion
from tqdm import tqdm

import utils
from Dataloader.dataLoader import OminiDataset_inference_w_all, reverse_axis_order
from OMorpher import OMorpher

# ========== CLI ==========

import argparse

parser = argparse.ArgumentParser()
parser.add_argument(
    "--config", "-C",
    help="Path for the config file",
    type=str,
    default="Config/config_om.yaml",
    required=False,
)
parser.add_argument(
    "--max-samples", "-N",
    help="Max number of subjects to include (0 = all)",
    type=int,
    default=0,
)
args = parser.parse_args()

# ========== Config ==========

with open(args.config, "r") as file:
    hyp_parameters = yaml.safe_load(file)
    print(hyp_parameters)

hyp_parameters["batchsize"] = 1
model_img_sz = hyp_parameters["img_size"]
timesteps = hyp_parameters["timesteps"]
condition_type = hyp_parameters["condition_type"]
ndims = hyp_parameters["ndims"]

# ========== Dataset ==========

label_keys = ["brain"]
database = ["Brats2019"]

dataset = OminiDataset_inference_w_all(
    transform=None, min_crop_ratio=1.0, label_key=label_keys, database=database,
)

# ========== OMorpher setup ==========

epoch = f'{hyp_parameters["model_id_str"]}_{hyp_parameters["data_name"]}_{hyp_parameters["net_name"]}'
model_save_path = os.path.join(
    f'Models/{hyp_parameters["data_name"]}_{hyp_parameters["net_name"]}/',
    str(epoch) + ".pth",
)
print("Loading model from:", model_save_path)

om = OMorpher(
    config=hyp_parameters,
    checkpoint_path=model_save_path,
    device=str(hyp_parameters.get("device", "cpu")),
)
print(om)

# ========== Output directories ==========

reg_img_savepath = hyp_parameters["reg_img_savepath"]
reg_msk_savepath = hyp_parameters["reg_msk_savepath"]
reg_ddf_savepath = hyp_parameters["reg_ddf_savepath"]

reg_img_savepath_fullres = reg_img_savepath.rstrip("/") + "_fullres/"
reg_msk_savepath_fullres = reg_msk_savepath.rstrip("/") + "_fullres/"
reg_ddf_savepath_fullres = reg_ddf_savepath.rstrip("/") + "_fullres/"

eval_dir = os.path.join(reg_img_savepath, "..", "eval")

for p in [
    reg_img_savepath, reg_msk_savepath, reg_ddf_savepath,
    reg_img_savepath_fullres, reg_msk_savepath_fullres, reg_ddf_savepath_fullres,
    eval_dir,
]:
    os.makedirs(p, exist_ok=True)

# ========== Settings ==========

skip_self = True  # skip pairs where source == target

# Labels that are NOT organs — excluded from metric evaluation.
# BraTS "brain" is actually a tumour segmentation (non-enhancing tumour, edema,
# enhancing tumour), not a whole-brain mask, so it must be excluded.
EXCLUDE_LABELS = {
    "brain",       # BraTS tumour segmentation
    "tumor",       # PSMA-CT / PSMA-FDG tumour
    "tumour",
    "noisy",       # Kaggle OSIC artefact mask
}
# Any label containing these substrings is also excluded
EXCLUDE_SUBSTRINGS = {"lesion", "tumor", "tumour"}


# ========== Helper functions ==========


def center_pad_to_cube(volume):
    """Pad volume to a cube using the max dimension, with symmetric (center) padding."""
    max_dim = max(volume.shape[:3])
    pad_width = []
    for s in volume.shape[:3]:
        total_pad = max_dim - s
        pad_before = total_pad // 2
        pad_after = total_pad - pad_before
        pad_width.append((pad_before, pad_after))
    for _ in range(volume.ndim - 3):
        pad_width.append((0, 0))
    return np.pad(volume, pad_width, mode="constant", constant_values=0)


def load_fullres_volume(key, ds):
    """Load original-resolution volume: axis reorder, clamp, normalize, center-pad to cube."""
    volume = sitk.ReadImage(key)
    volume = sitk.GetArrayFromImage(volume)
    volume = reverse_axis_order(volume)
    if volume.ndim == 4:
        channel_ids = ds.get_channel_ids(key)
        channel_id = channel_ids[0] if len(channel_ids) > 0 else 0
        volume = volume[:, :, :, channel_id]
    if ds.clamp_range is not None:
        modality = ds.ALLdata_filtered[key].get("Modality", None)
        if modality == "CT":
            volume = np.clip(volume, ds.clamp_range[0], ds.clamp_range[1])
    volume = ds.normalize(volume)
    volume = center_pad_to_cube(volume)
    return volume


def load_fullres_label(key, ds, label_key):
    """Load original-resolution label: axis reorder, center-pad to cube."""
    label_path_dict = ds.ALLdata_filtered[key].get("Label_path", {})
    task_labels = label_path_dict.get("segmentation", {})
    if label_key not in task_labels:
        return None
    label = sitk.ReadImage(task_labels[label_key])
    label = sitk.GetArrayFromImage(label)
    label = reverse_axis_order(label)
    if label.ndim > 3:
        channel_ids = ds.get_channel_ids(key)
        if len(channel_ids) != 0:
            label = label[..., channel_ids]
    label = center_pad_to_cube(label)
    return label


def get_volume_name(key):
    """Extract a short name from a NIfTI file path."""
    name = os.path.basename(key)
    for ext in [".nii.gz", ".nii"]:
        if name.endswith(ext):
            name = name[: -len(ext)]
            break
    return name


def is_organ_label(label_key):
    """Return True if label_key is an organ (not tumour/lesion)."""
    lk_lower = label_key.lower()
    if lk_lower in EXCLUDE_LABELS:
        return False
    return not any(kw in lk_lower for kw in EXCLUDE_SUBSTRINGS)


# ---------- Evaluation metrics ----------


def _surface_distances(pred, gt):
    """Compute directed surface distances between two binary masks.



    Returns (dist_pred_to_gt, dist_gt_to_pred) arrays, or (None, None)

    if either mask is empty or has no extractable surface.

    """
    pred_bool = pred > 0.5
    gt_bool = gt > 0.5

    if not np.any(pred_bool) or not np.any(gt_bool):
        return None, None

    # Extract surface voxels via erosion
    struct = None  # default 3x3(x3) cross connectivity
    pred_surface = pred_bool ^ binary_erosion(pred_bool, structure=struct)
    gt_surface = gt_bool ^ binary_erosion(gt_bool, structure=struct)

    # Fallback: single-voxel regions lose their surface after erosion
    if not np.any(pred_surface):
        pred_surface = pred_bool
    if not np.any(gt_surface):
        gt_surface = gt_bool

    dt_gt = distance_transform_edt(~gt_surface)
    dt_pred = distance_transform_edt(~pred_surface)

    return dt_gt[pred_surface], dt_pred[gt_surface]


def compute_dsc(pred, gt):
    """Dice Similarity Coefficient."""
    pred_bool = pred > 0.5
    gt_bool = gt > 0.5
    intersection = np.sum(pred_bool & gt_bool)
    denom = np.sum(pred_bool) + np.sum(gt_bool)
    if denom == 0:
        return 1.0  # both empty — perfect agreement
    return 2.0 * float(intersection) / float(denom)


def compute_asd(pred, gt):
    """Average (symmetric) Surface Distance."""
    d1, d2 = _surface_distances(pred, gt)
    if d1 is None:
        return float("nan")
    return (np.mean(d1) + np.mean(d2)) / 2.0


def compute_hd(pred, gt):
    """Hausdorff Distance (maximum of directed HDs)."""
    d1, d2 = _surface_distances(pred, gt)
    if d1 is None:
        return float("nan")
    return float(max(np.max(d1), np.max(d2)))


def compute_negdetj_pct(ddf, ndims=3):
    """Percent of voxels with negative Jacobian determinant.



    Args:

        ddf: displacement field tensor [1, ndims, ...] or numpy array.

        ndims: 2 or 3.

    Returns:

        Percentage of voxels where det(Jacobian) < 0.

    """
    if isinstance(ddf, torch.Tensor):
        ddf = ddf.detach().cpu().numpy()
    if ddf.ndim == ndims + 2:
        ddf = ddf[0]  # remove batch dim -> [C, ...]

    if ndims == 3:
        dux_dx = np.diff(ddf[0], axis=0, append=ddf[0, -1:, :, :])
        duy_dx = np.diff(ddf[1], axis=0, append=ddf[1, -1:, :, :])
        duz_dx = np.diff(ddf[2], axis=0, append=ddf[2, -1:, :, :])

        dux_dy = np.diff(ddf[0], axis=1, append=ddf[0, :, -1:, :])
        duy_dy = np.diff(ddf[1], axis=1, append=ddf[1, :, -1:, :])
        duz_dy = np.diff(ddf[2], axis=1, append=ddf[2, :, -1:, :])

        dux_dz = np.diff(ddf[0], axis=2, append=ddf[0, :, :, -1:])
        duy_dz = np.diff(ddf[1], axis=2, append=ddf[1, :, :, -1:])
        duz_dz = np.diff(ddf[2], axis=2, append=ddf[2, :, :, -1:])

        j11 = 1.0 + dux_dx; j12 = dux_dy; j13 = dux_dz
        j21 = duy_dx; j22 = 1.0 + duy_dy; j23 = duy_dz
        j31 = duz_dx; j32 = duz_dy; j33 = 1.0 + duz_dz

        detj = (
            j11 * (j22 * j33 - j23 * j32)
            - j12 * (j21 * j33 - j23 * j31)
            + j13 * (j21 * j32 - j22 * j31)
        )
    elif ndims == 2:
        dux_dx = np.diff(ddf[0], axis=0, append=ddf[0, -1:, :])
        duy_dx = np.diff(ddf[1], axis=0, append=ddf[1, -1:, :])

        dux_dy = np.diff(ddf[0], axis=1, append=ddf[0, :, -1:])
        duy_dy = np.diff(ddf[1], axis=1, append=ddf[1, :, -1:])

        detj = (1.0 + dux_dx) * (1.0 + duy_dy) - dux_dy * duy_dx
    else:
        raise ValueError(f"Unsupported ndims={ndims}")

    n_neg = np.sum(detj < 0)
    n_total = detj.size
    return 100.0 * float(n_neg) / float(n_total)


# ========== Pre-load all subjects ==========

keys = list(dataset.ALLdata_filtered.keys())
if args.max_samples > 0:
    keys = keys[: args.max_samples]
print(f"Total subjects: {len(keys)} (max_samples={args.max_samples or 'all'})")

subjects = []
for key in tqdm(keys, desc="Loading subjects"):
    fullres_vol = load_fullres_volume(key, dataset)
    om.set_init_img(fullres_vol)
    img_model = om._init_img.clone()
    img_fullres = om._init_img_raw.clone()
    orig_sz = list(img_fullres.shape[2:])

    masks_model = []
    masks_fullres = []
    for lk in label_keys:
        lab = load_fullres_label(key, dataset, lk)
        model_t, fullres_t = om._standardize_label(lab)
        masks_model.append(model_t)
        masks_fullres.append(fullres_t)

    if masks_model:
        mask_model = torch.cat(masks_model, dim=1)
        mask_fullres = torch.cat(masks_fullres, dim=1)
    else:
        mask_model = None
        mask_fullres = None

    subjects.append({
        "key": key,
        "img_model": img_model,
        "img_fullres": img_fullres,
        "mask_model": mask_model,
        "mask_fullres": mask_fullres,
        "orig_sz": orig_sz,
    })

print(f"Loaded {len(subjects)} subjects into memory.")

# ========== Prepare evaluation structures ==========

vol_names = [get_volume_name(subj["key"]) for subj in subjects]

# Disambiguate duplicate basenames by appending index
_seen = {}
for i, vn in enumerate(vol_names):
    _seen.setdefault(vn, []).append(i)
for vn, indices in _seen.items():
    if len(indices) > 1:
        for idx in indices:
            vol_names[idx] = f"{vn}_{idx}"

organ_label_indices = []  # (channel_index, label_key) for organ labels only
for c, lk in enumerate(label_keys):
    if is_organ_label(lk):
        organ_label_indices.append((c, lk))

if organ_label_indices:
    print(f"Organ labels for evaluation: {[lk for _, lk in organ_label_indices]}")
else:
    print("No organ labels found — skipping evaluation metrics.")

# metrics[label_key][metric_name][(t, s)] = value
metrics = {
    lk: {"dsc": {}, "asd": {}, "hd": {}}
    for _, lk in organ_label_indices
}

# Per-pair DDF quality metric
negdetj_pct = {}  # (t, s) -> percentage of negative Jacobian determinant

# ========== All-to-all registration ==========

with torch.no_grad():
    for t, tgt in enumerate(tqdm(subjects, desc="Targets")):
        tgt_tag = f"Tgt{t:04d}"

        # --- Save target original at model resolution ---
        nib.save(
            utils.converet_to_nibabel(tgt["img_model"], ndims=ndims),
            os.path.join(reg_img_savepath, f"{tgt_tag}_ORG.nii.gz"),
        )
        if tgt["mask_model"] is not None:
            nib.save(
                utils.converet_to_nibabel(tgt["mask_model"], ndims=ndims),
                os.path.join(reg_msk_savepath, f"{tgt_tag}_ORG_GT.nii.gz"),
            )

        # --- Save target original at full resolution ---
        nib.save(
            utils.converet_to_nibabel(tgt["img_fullres"], ndims=ndims),
            os.path.join(reg_img_savepath_fullres, f"{tgt_tag}_ORG.nii.gz"),
        )
        if tgt["mask_fullres"] is not None:
            nib.save(
                utils.converet_to_nibabel(tgt["mask_fullres"], ndims=ndims),
                os.path.join(reg_msk_savepath_fullres, f"{tgt_tag}_ORG_GT.nii.gz"),
            )

        # --- Inner loop: register each source to this target ---
        for s, src in enumerate(subjects):
            if skip_self and s == t:
                continue

            pair_tag = f"Tgt{t:04d}_Src{s:04d}"
            print(f"  Registering {pair_tag}")

            om.set_init_img(src["img_model"])
            om.set_cond_img(tgt["img_model"].clone().detach())

            om.predict(
                T=[None, timesteps],
                proc_type=condition_type,
            )

            ddf_comp = om.get_def()

            # --- DDF quality: percent negative Jacobian determinant ---
            neg_pct = compute_negdetj_pct(ddf_comp, ndims=ndims)
            negdetj_pct[(t, s)] = neg_pct
            print(f"    %|J|<0 = {neg_pct:.4f}%")

            # --- Model-resolution registered image ---
            img_rec = om.apply_def(
                img=src["img_model"], ddf=ddf_comp, padding_mode="zeros",
            )
            nib.save(
                utils.converet_to_nibabel(img_rec, ndims=ndims),
                os.path.join(reg_img_savepath, f"{pair_tag}.nii.gz"),
            )

            # --- Model-resolution registered mask ---
            msk_rec = None
            if src["mask_model"] is not None:
                msk_rec = om.apply_def(
                    img=src["mask_model"], ddf=ddf_comp,
                    padding_mode="zeros", resample_mode="nearest",
                )
                nib.save(
                    utils.converet_to_nibabel(msk_rec, ndims=ndims),
                    os.path.join(reg_msk_savepath, f"{pair_tag}_GT.nii.gz"),
                )

            # --- Model-resolution DDF ---
            nib.save(
                utils.converet_to_nibabel(ddf_comp, ndims=ndims),
                os.path.join(reg_ddf_savepath, f"{pair_tag}.nii.gz"),
            )

            # --- Full-resolution registered image ---
            img_rec_fullres = om.apply_def(
                img=src["img_fullres"], ddf=ddf_comp, padding_mode="border",
            )
            nib.save(
                utils.converet_to_nibabel(img_rec_fullres, ndims=ndims),
                os.path.join(reg_img_savepath_fullres, f"{pair_tag}.nii.gz"),
            )

            # --- Full-resolution registered mask ---
            msk_rec_fullres = None
            if src["mask_fullres"] is not None:
                msk_rec_fullres = om.apply_def(
                    img=src["mask_fullres"], ddf=ddf_comp,
                    padding_mode="zeros", resample_mode="nearest",
                )
                nib.save(
                    utils.converet_to_nibabel(msk_rec_fullres, ndims=ndims),
                    os.path.join(reg_msk_savepath_fullres, f"{pair_tag}_GT.nii.gz"),
                )

            # --- Full-resolution DDF ---
            ddf_fullres = F.interpolate(
                ddf_comp, size=src["orig_sz"], mode="trilinear", align_corners=False,
            )
            nib.save(
                utils.converet_to_nibabel(ddf_fullres, ndims=ndims),
                os.path.join(reg_ddf_savepath_fullres, f"{pair_tag}.nii.gz"),
            )

            # --- Evaluation metrics (full-res organ labels) ---
            if (
                organ_label_indices
                and msk_rec_fullres is not None
                and tgt["mask_fullres"] is not None
            ):
                for c, lk in organ_label_indices:
                    tgt_mask_np = tgt["mask_fullres"][0, c].cpu().numpy()
                    reg_mask_np = msk_rec_fullres[0, c].cpu().numpy()

                    # Skip placeholder masks (fill_value = -1)
                    if np.all(tgt_mask_np < 0) or np.all(reg_mask_np < 0):
                        continue

                    dsc_val = compute_dsc(reg_mask_np, tgt_mask_np)
                    asd_val = compute_asd(reg_mask_np, tgt_mask_np)
                    hd_val = compute_hd(reg_mask_np, tgt_mask_np)

                    metrics[lk]["dsc"][(t, s)] = dsc_val
                    metrics[lk]["asd"][(t, s)] = asd_val
                    metrics[lk]["hd"][(t, s)] = hd_val

                    print(
                        f"    [{lk}] DSC={dsc_val:.4f}  "
                        f"ASD={asd_val:.2f}  HD={hd_val:.2f}"
                    )

print("All-to-all registration complete.")

# ========== Write evaluation CSVs ==========

n_subj = len(subjects)

# --- %|J|<0 matrix CSV ---
negdetj_csv_path = os.path.join(eval_dir, "negdetj_pct.csv")
with open(negdetj_csv_path, "w", newline="") as f:
    writer = csv.writer(f)
    writer.writerow(["target \\ source"] + vol_names)
    for t_idx in range(n_subj):
        row = [vol_names[t_idx]]
        for s_idx in range(n_subj):
            val = negdetj_pct.get((t_idx, s_idx))
            if val is None:
                row.append("")
            else:
                row.append(f"{val:.6f}")
        writer.writerow(row)
print(f"Saved {negdetj_csv_path}")

for c, lk in organ_label_indices:
    # Use label prefix only when there are multiple organ labels
    prefix = f"{lk}_" if len(organ_label_indices) > 1 else ""

    for metric_name in ["dsc", "asd", "hd"]:
        csv_path = os.path.join(eval_dir, f"{prefix}{metric_name}.csv")
        with open(csv_path, "w", newline="") as f:
            writer = csv.writer(f)
            # Header row: empty corner cell + source volume names
            writer.writerow(["target \\ source"] + vol_names)
            for t in range(n_subj):
                row = [vol_names[t]]
                for s in range(n_subj):
                    val = metrics[lk][metric_name].get((t, s))
                    if val is None:
                        row.append("")  # self-pair or missing
                    elif np.isnan(val):
                        row.append("NaN")
                    else:
                        row.append(f"{val:.6f}")
                writer.writerow(row)
        print(f"Saved {csv_path}")

# --- Overall summary ---
overall_path = os.path.join(eval_dir, "overall.csv")
with open(overall_path, "w", newline="") as f:
    writer = csv.writer(f)
    writer.writerow(["label", "metric", "mean", "std", "n_pairs"])
    # %|J|<0 summary (not per-label)
    negdetj_vals = [v for v in negdetj_pct.values() if not np.isnan(v)]
    if negdetj_vals:
        writer.writerow([
            "ALL", "%|J|<0",
            f"{np.mean(negdetj_vals):.6f}", f"{np.std(negdetj_vals):.6f}",
            len(negdetj_vals),
        ])
    for _, lk in organ_label_indices:
        for metric_name in ["dsc", "asd", "hd"]:
            vals = [
                v for v in metrics[lk][metric_name].values()
                if not np.isnan(v)
            ]
            if vals:
                mean_val = np.mean(vals)
                std_val = np.std(vals)
                n_pairs = len(vals)
            else:
                mean_val = float("nan")
                std_val = float("nan")
                n_pairs = 0
            writer.writerow([
                lk,
                metric_name.upper(),
                f"{mean_val:.6f}" if not np.isnan(mean_val) else "NaN",
                f"{std_val:.6f}" if not np.isnan(std_val) else "NaN",
                n_pairs,
            ])
print(f"Saved {overall_path}")