{
  "_meta": {
    "title": "AdipoNeuroMap reference parameters",
    "note": "Research/reference values compiled from adipose tissue clearing & imaging literature. Order-of-magnitude guidance for synthetic-demo calibration, NOT clinical thresholds.",
    "disclaimer": "Research/reference use only - not a clinical diagnostic tool.",
    "version": "2026-06-01"
  },
  "adipocyte_size_classes_um": {
    "_definition": "Adipocyte equivalent-sphere diameter (um). White adipocytes are large lipid-laden cells; brown/beige are smaller multilocular.",
    "classes": [
      {"label": "small",       "min_um": 20.0,  "max_um": 50.0,  "typical_depot": "BAT/beige, fasted iWAT"},
      {"label": "medium",      "min_um": 50.0,  "max_um": 90.0,  "typical_depot": "lean iWAT/eWAT"},
      {"label": "large",       "min_um": 90.0,  "max_um": 130.0, "typical_depot": "obese iWAT"},
      {"label": "hypertrophic","min_um": 130.0, "max_um": 220.0, "typical_depot": "obese eWAT (insulin-resistant)"}
    ]
  },
  "sympathetic_axon_density_mm_per_mm3": {
    "_definition": "TH+ sympathetic axon length per tissue volume (mm of axon per mm^3). Higher in thermogenic depots.",
    "ranges_by_depot": {
      "BAT":  {"low": 200.0, "normal_mid": 600.0, "high": 1200.0, "note": "densely innervated, thermogenic"},
      "iWAT": {"low": 30.0,  "normal_mid": 120.0, "high": 300.0,  "note": "moderate, beiging-responsive"},
      "eWAT": {"low": 10.0,  "normal_mid": 45.0,  "high": 110.0,  "note": "sparse; declines with obesity"}
    },
    "branch_point_density_per_mm3": {"low": 50.0, "normal_mid": 400.0, "high": 1500.0},
    "mean_segment_length_um": {"short": 15.0, "typical": 40.0, "long": 90.0}
  },
  "cls_definition": {
    "_definition": "Crown-like structure: ring/shell of F4/80+ macrophages surrounding a dead or dying adipocyte. Marker of adipose inflammation.",
    "min_macrophages_in_ring": 3,
    "ring_completeness_fraction_min": 0.5,
    "density_per_mm2_section": {"lean": 0.5, "elevated": 3.0, "high": 8.0},
    "density_per_mm3_volume": {"lean": 2.0, "elevated": 20.0, "high": 60.0},
    "clustering_index_note": "Nearest-neighbour ratio <1 indicates spatial clustering (focal inflammation); ~1 random; >1 dispersed."
  },
  "neuro_adipocyte_proximity": {
    "_definition": "Fraction of adipocytes whose centroid lies within a contact radius of a TH+ axon (neuro-adipose junction proxy).",
    "contact_radius_um": 25.0,
    "innervated_fraction_reference": {"BAT": 0.85, "iWAT": 0.45, "eWAT": 0.20}
  },
  "autofluorescence": {
    "_note": "Adipose tissue has strong broadband autofluorescence (lipofuscin, lipid). Background suppression via rolling-ball / top-hat before segmentation.",
    "tophat_radius_voxels": 12,
    "background_percentile": 25.0
  }
}