{
  "description": "Reference parameters for design-based stereology and islet morphometry. Used by PancreaClear3D for the 2D-vs-3D bias mode and islet size-class binning. Values are representative literature ranges for adult mouse pancreas; treat as illustrative defaults, not validated constants.",
  "disclaimer": "Research/reference use only - NOT a clinical diagnostic device.",
  "cavalieri": {
    "method": "Cavalieri principle (volume = sum of section areas x section spacing)",
    "section_spacing_um_default": 50.0,
    "physical_disector_height_um": 25.0,
    "smith_guttman_correction": "object count via disector avoids Abercrombie/Floderus 2D oversizing bias",
    "note": "2D systematic-uniform-random sampling underestimates large/sparse objects and can over/under-estimate total beta-mass depending on islet size distribution and section spacing."
  },
  "islet_size_classes_um_diameter": [
    {"name": "very_small", "min": 20.0,  "max": 50.0},
    {"name": "small",      "min": 50.0,  "max": 100.0},
    {"name": "medium",     "min": 100.0, "max": 200.0},
    {"name": "large",      "min": 200.0, "max": 350.0},
    {"name": "very_large", "min": 350.0, "max": 700.0}
  ],
  "zonal_regions": [
    {"name": "head", "axis_fraction_min": 0.0,  "axis_fraction_max": 0.34},
    {"name": "body", "axis_fraction_min": 0.34, "axis_fraction_max": 0.67},
    {"name": "tail", "axis_fraction_min": 0.67, "axis_fraction_max": 1.0}
  ],
  "zonal_islet_density_note": "In rodent/human pancreas the splenic tail is typically richer in islets than the head; PancreaClear3D quantifies the observed gradient per sample.",
  "composition_reference": {
    "beta_fraction_typical": 0.75,
    "alpha_fraction_typical": 0.18,
    "note": "beta:alpha ratio ~3-4:1 in healthy adult mouse islets; shifts toward alpha in T1D/T2D models."
  },
  "vascular_neural": {
    "cd31_marker": "PECAM-1 / CD31 endothelial (islet microvasculature)",
    "th_marker": "tyrosine hydroxylase (sympathetic axons)",
    "cgrp_marker": "calcitonin gene-related peptide (sensory axons)",
    "proximity_threshold_um_default": 15.0,
    "note": "islets are densely vascularized (~5-10x exocrine capillary density) and receive autonomic/sensory innervation; proximity quantified as fraction of islet surface voxels within threshold of a marker-positive voxel."
  },
  "synthetic_demo_defaults": {
    "volume_shape_zyx": [60, 160, 160],
    "voxel_size_um": 8.0,
    "n_islets": 70,
    "size_distribution": "log-uniform spanning ~4 decades of volume (small to very_large)",
    "head_body_tail_density_gradient": [0.7, 1.0, 1.6],
    "seed_default": 7
  }
}