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/* Copyright (c) 2008-2025 the MRtrix3 contributors.
*
* This Source Code Form is subject to the terms of the Mozilla Public
* License, v. 2.0. If a copy of the MPL was not distributed with this
* file, You can obtain one at http://mozilla.org/MPL/2.0/.
*
* Covered Software is provided under this License on an "as is"
* basis, without warranty of any kind, either expressed, implied, or
* statutory, including, without limitation, warranties that the
* Covered Software is free of defects, merchantable, fit for a
* particular purpose or non-infringing.
* See the Mozilla Public License v. 2.0 for more details.
*
* For more details, see http://www.mrtrix.org/.
*/
#include "command.h"
#include "image.h"
#include "algo/loop.h"
#include "transform.h"
#include "math/least_squares.h"
#include "algo/threaded_copy.h"
#include "adapter/replicate.h"
using namespace MR;
using namespace App;
#define DEFAULT_REFERENCE_VALUE 0.28209479177
#define DEFAULT_MAIN_ITER_VALUE 15
#define DEFAULT_BALANCE_MAXITER_VALUE 7
#define DEFAULT_POLY_ORDER 3
const char* poly_order_choices[] = { "0", "1", "2", "3", nullptr };
void usage ()
{
AUTHOR = "Thijs Dhollander (thijs.dhollander@gmail.com), Rami Tabbara (rami.tabbara@florey.edu.au), "
"David Raffelt (david.raffelt@florey.edu.au), Jonas Rosnarho-Tornstrand (jonas.rosnarho-tornstrand@kcl.ac.uk) "
"and J-Donald Tournier (jdtournier@gmail.com)";
SYNOPSIS = "Multi-tissue informed log-domain intensity normalisation";
DESCRIPTION
+ "This command takes as input any number of tissue components (e.g. from "
"multi-tissue CSD) and outputs corresponding normalised tissue components "
"corrected for the effects of (residual) intensity inhomogeneities. "
"Intensity normalisation is performed by optimising the voxel-wise sum of "
"all tissue compartments towards a constant value, under constraints of "
"spatial smoothness (polynomial basis of a given order). Different to "
"the Raffelt et al. 2017 abstract, this algorithm performs this task "
"in the log-domain instead, with added gradual outlier rejection, different "
"handling of the balancing factors between tissue compartments and a "
"different iteration structure."
+ "The -mask option is mandatory and is optimally provided with a brain mask "
"(such as the one obtained from dwi2mask earlier in the processing pipeline). "
"Outlier areas with exceptionally low or high combined tissue contributions are "
"accounted for and reoptimised as the intensity inhomogeneity estimation becomes "
"more accurate.";
EXAMPLES
+ Example ("Default usage (for 3-tissue CSD compartments)",
"mtnormalise wmfod.mif wmfod_norm.mif gm.mif gm_norm.mif csf.mif csf_norm.mif -mask mask.mif",
"Note how for each tissue compartment, the input and output images are provided as "
"a consecutive pair.");
ARGUMENTS
+ Argument ("input output", "list of all input and output tissue compartment files (see example usage).").type_various().allow_multiple();
OPTIONS
+ Option ("mask", "the mask defines the data used to compute the intensity normalisation. This option is mandatory.").required ()
+ Argument ("image").type_image_in ()
+ Option ("order", "the maximum order of the polynomial basis used to fit the normalisation field in the log-domain. "
"An order of 0 is equivalent to not allowing spatial variance of the intensity normalisation factor. "
"(default: " + str(DEFAULT_POLY_ORDER) + ")")
+ Argument ("number").type_choice (poly_order_choices)
+ Option ("niter", "set the number of iterations. The first (and potentially only) entry applies to the main loop. "
"If supplied as a comma-separated list of integers, the second entry applies to the inner loop to update the balance factors "
"(default: " + str(DEFAULT_MAIN_ITER_VALUE) + "," + str(DEFAULT_BALANCE_MAXITER_VALUE) + ").")
+ Argument ("number").type_sequence_int()
+ Option ("reference", "specify the (positive) reference value to which the summed tissue compartments will be normalised. "
"(default: " + str(DEFAULT_REFERENCE_VALUE, 6) + ", SH DC term for unit angular integral)")
+ Argument ("number").type_float (std::numeric_limits<default_type>::min())
+ Option ("balanced", "incorporate the per-tissue balancing factors into scaling of the output images "
"(NOTE: use of this option has critical consequences for AFD intensity normalisation; "
"should not be used unless these consequences are fully understood)")
+ OptionGroup ("Debugging options")
+ Option ("check_norm", "output the final estimated spatially varying intensity level that is used for normalisation.")
+ Argument ("image").type_image_out ()
+ Option ("check_mask", "output the final mask used to compute the normalisation. "
"This mask excludes regions identified as outliers by the optimisation process.")
+ Argument ("image").type_image_out ()
+ Option ("check_factors", "output the tissue balance factors computed during normalisation.")
+ Argument ("file").type_file_out ();
REFERENCES
+ "Raffelt, D.; Dhollander, T.; Tournier, J.-D.; Tabbara, R.; Smith, R. E.; Pierre, E. & Connelly, A. " // Internal
"Bias Field Correction and Intensity Normalisation for Quantitative Analysis of Apparent Fibre Density. "
"In Proc. ISMRM, 2017, 26, 3541"
+ "Dhollander, T.; Tabbara, R.; Rosnarho-Tornstrand, J.; Tournier, J.-D.; Raffelt, D. & Connelly, A. " // Internal
"Multi-tissue log-domain intensity and inhomogeneity normalisation for quantitative apparent fibre density. "
"In Proc. ISMRM, 2021, 29, 2472";
;
}
using ValueType = float;
using ImageType = Image<ValueType>;
using MaskType = Image<bool>;
using IndexType = Image<uint32_t>;
// Function to get the number of basis vectors based on the desired order
int num_basis_vec_for_order (int order)
{
switch (order) {
case 0: return 1;
case 1: return 4;
case 2: return 10;
default: return 20;
}
assert (false);
return -1;
};
// Struct to get user specified number of basis functions
struct PolyBasisFunction { MEMALIGN (PolyBasisFunction)
PolyBasisFunction(const int order) :
n_basis_vecs (num_basis_vec_for_order (order)) { };
const int n_basis_vecs;
FORCE_INLINE Eigen::VectorXd operator () (const Eigen::Vector3d& pos) const {
double x = pos[0];
double y = pos[1];
double z = pos[2];
Eigen::VectorXd basis (n_basis_vecs);
basis(0) = 1.0;
if (n_basis_vecs < 4)
return basis;
basis(1) = x;
basis(2) = y;
basis(3) = z;
if (n_basis_vecs < 10)
return basis;
basis(4) = x * x;
basis(5) = y * y;
basis(6) = z * z;
basis(7) = x * y;
basis(8) = x * z;
basis(9) = y * z;
if (n_basis_vecs < 20)
return basis;
basis(10) = x * x * x;
basis(11) = y * y * y;
basis(12) = z * z * z;
basis(13) = x * x * y;
basis(14) = x * x * z;
basis(15) = y * y * x;
basis(16) = y * y * z;
basis(17) = z * z * x;
basis(18) = z * z * y;
basis(19) = x * y * z;
return basis;
}
};
IndexType index_mask_voxels (size_t& num_voxels)
{
auto opt = get_options ("mask");
auto mask = MaskType::open (opt[0][0]);
check_effective_dimensionality (mask, 3);
if (voxel_count (mask, 0, 3) >= std::numeric_limits<uint32_t>::max()-1)
throw Exception ("mask size exceeds maximum supported using 32-bit integer");
num_voxels = 0;
Header header (mask);
header.ndim() = 3;
header.datatype() = DataType::UInt32;
IndexType index = IndexType::scratch (header, "index");
for (auto l = Loop(0, 3) (mask, index); l; ++l) {
if (mask.value())
index.value() = num_voxels++;
else
index.value() = std::numeric_limits<uint32_t>::max();
}
if (!num_voxels)
throw Exception ("Mask contains no valid voxels.");
INFO ("mask image contains " + str(num_voxels) + " voxels");
return index;
}
Eigen::MatrixXd initialise_basis (IndexType& index, size_t num_voxels, int order)
{
struct BasisInitialiser { NOMEMALIGN
BasisInitialiser (const Transform& transform, const PolyBasisFunction& basis_function, Eigen::MatrixXd& basis) :
basis_function (basis_function),
transform (transform),
basis (basis) { }
void operator() (IndexType& index) {
const uint32_t idx = index.value();
if (idx != std::numeric_limits<uint32_t>::max()) {
assert (idx < basis.rows());
Eigen::Vector3d vox (index.index(0), index.index(1), index.index(2));
Eigen::Vector3d pos = transform.voxel2scanner * vox;
basis.row(idx) = basis_function (pos);
}
}
const PolyBasisFunction& basis_function;
const Transform& transform;
Eigen::MatrixXd& basis;
};
INFO ("initialising basis...");
PolyBasisFunction basis_function (order);
Transform transform (index);
Eigen::MatrixXd basis (num_voxels, num_basis_vec_for_order (order));
ThreadedLoop (index, 0, 3, 2).run (BasisInitialiser (transform, basis_function, basis), index);
return basis;
}
void load_data (Eigen::MatrixXd& data, const std::string& image_name, IndexType& index)
{
static int num = 0;
auto in = ImageType::open (image_name);
check_dimensions (index, in, 0, 3);
struct Loader { NOMEMALIGN
public:
Loader (Eigen::MatrixXd& data, int num) : data (data), num (num) { }
void operator() (ImageType& in, IndexType& index) {
const uint32_t idx = index.value();
if (idx != std::numeric_limits<uint32_t>::max())
data(idx, num) = std::max<ValueType> (in.value(), 0.0);
}
Eigen::MatrixXd& data;
const int num;
};
ThreadedLoop (in, 0, 3, 2).run (Loader (data, num), in, index);
++num;
}
inline bool lessthan_NaN (const double& a, const double& b) {
if (std::isnan (a))
return true;
if (std::isnan (b))
return false;
return a<b;
}
size_t detect_outliers (
double outlier_range,
const Eigen::MatrixXd& data,
const Eigen::VectorXd& field,
const Eigen::VectorXd& balance_factors,
Eigen::VectorXd& weights)
{
Eigen::VectorXd summed_log = (data * balance_factors).cwiseQuotient (field).array().log();
Eigen::VectorXd summed_log_sorted = summed_log;
const size_t lower_quartile_idx = std::round (field.size() * 0.25);
const size_t upper_quartile_idx = std::round (field.size() * 0.75);
std::nth_element (summed_log_sorted.data(), summed_log_sorted.data() + lower_quartile_idx,
summed_log_sorted.data() + summed_log_sorted.size(), lessthan_NaN);
double lower_quartile = summed_log_sorted[lower_quartile_idx];
std::nth_element (summed_log_sorted.data(), summed_log_sorted.data() + upper_quartile_idx,
summed_log_sorted.data() + summed_log_sorted.size(), lessthan_NaN);
double upper_quartile = summed_log_sorted[upper_quartile_idx];
INFO (" outlier rejection quartiles: [ " + str(lower_quartile) + " " + str(upper_quartile) + " ]");
double lower_outlier_threshold = lower_quartile - outlier_range * (upper_quartile - lower_quartile);
double upper_outlier_threshold = upper_quartile + outlier_range * (upper_quartile - lower_quartile);
struct SetWeight { NOMEMALIGN
size_t& changed;
const double lower_outlier_threshold, upper_outlier_threshold;
double operator() (double v, double w) const {
v = std::isfinite (v) && v >= lower_outlier_threshold && v <= upper_outlier_threshold;
if (v != w)
++changed;
return v;
}
};
size_t changed = 0;
SetWeight set_weight = { changed, lower_outlier_threshold, upper_outlier_threshold };
weights = summed_log.binaryExpr (weights, set_weight);
return changed;
}
void compute_balance_factors (
const Eigen::MatrixXd& data,
const Eigen::VectorXd& field,
const Eigen::VectorXd& weights,
Eigen::VectorXd& balance_factors)
{
Eigen::MatrixXd scaled_data = data.transpose().array().rowwise() / field.transpose().array();
for (ssize_t n = 0; n < scaled_data.cols(); ++n) {
if (!weights[n])
scaled_data.col(n).array() = 0.0;
}
Eigen::MatrixXd HtH (data.cols(), data.cols());
HtH.triangularView<Eigen::Lower>() = scaled_data * scaled_data.transpose();
Eigen::LLT<Eigen::MatrixXd> llt;
balance_factors.noalias() = llt.compute (HtH.triangularView<Eigen::Lower>()).solve (scaled_data * Eigen::VectorXd::Ones(field.size()));
// Ensure our balance factors satisfy the condition that sum(log(balance_factors)) = 0
if (!balance_factors.allFinite() || (balance_factors.array() <= 0.0).any())
throw Exception ("Non-positive tissue balance factor was computed."
" Balance factors: " + str(balance_factors.transpose()));
balance_factors /= std::exp (balance_factors.array().log().sum() / data.cols());
}
void update_field (
const double log_norm_value,
const Eigen::MatrixXd& basis,
const Eigen::MatrixXd& data,
const Eigen::VectorXd& balance_factors,
const Eigen::VectorXd& weights,
Eigen::VectorXd& field_coeffs,
Eigen::VectorXd& field)
{
struct LogWeight { NOMEMALIGN
double operator() (double sum, double weight) const {
return sum > 0.0 ? weight * (std::log(sum) - log_norm_value) : 0.0;
}
const double log_norm_value;
};
LogWeight logweight = { log_norm_value };
Eigen::VectorXd logsum = data * balance_factors;
logsum = logsum.binaryExpr (weights, logweight);
Eigen::MatrixXd HtH = Eigen::MatrixXd::Zero (basis.cols(), basis.cols());
HtH.selfadjointView<Eigen::Lower>().rankUpdate ((basis.transpose().array().rowwise() * weights.transpose().array()).matrix());
Eigen::LLT<Eigen::MatrixXd> llt;
field_coeffs.noalias() = llt.compute (HtH.selfadjointView<Eigen::Lower>()).solve (basis.transpose() * logsum);
field.noalias() = (basis * field_coeffs).array().exp().matrix();
}
ImageType compute_full_field (int order, const Eigen::VectorXd& field_coeffs, const IndexType& index)
{
Header header (index);
header.datatype() = DataType::Float32;
auto out = ImageType::scratch (header, "full field");
Transform transform (out);
struct FieldWriter { NOMEMALIGN
void operator() (ImageType& field) const {
Eigen::Vector3d vox (field.index(0), field.index(1), field.index(2));
Eigen::Vector3d pos = transform.voxel2scanner * vox;
field.value() = std::exp (basis_function (pos).dot (field_coeffs));
}
const PolyBasisFunction& basis_function;
const Eigen::VectorXd& field_coeffs;
const Transform& transform;
};
PolyBasisFunction basis_function (order);
FieldWriter writer = { basis_function, field_coeffs, transform };
ThreadedLoop (out, 0, 3).run (writer, out);
return out;
}
void write_weights (const Eigen::VectorXd& data, IndexType& index, const std::string& output_file_name)
{
Header header (index);
header.datatype() = DataType::Float32;
auto out = ImageType::create (output_file_name, header);
struct Write { NOMEMALIGN
void operator() (ImageType& out, IndexType& index) const {
const uint32_t idx = index.value();
if (idx != std::numeric_limits<uint32_t>::max()) {
out.value() = data[idx];
}
}
const Eigen::VectorXd& data;
} write = { data };
ThreadedLoop (index, 0, 3).run (write, out, index);
}
void write_output (
const std::string& original,
const std::string& corrected,
bool output_balanced,
double balance_factor,
ImageType& field,
double lognorm_scale)
{
using ReplicatorType = Adapter::Replicate<ImageType>;
struct Scaler { NOMEMALIGN
void operator() (ImageType& original, ImageType& corrected, ReplicatorType& field) const {
corrected.value() = balance_factor * original.value() / field.value();
}
const double balance_factor;
};
auto in = ImageType::open (original);
Header header (in);
header.datatype() = DataType::Float32;
header.keyval()["lognorm_scale"] = str(lognorm_scale);
if (output_balanced)
header.keyval()["lognorm_balance"] = str(balance_factor);
else
balance_factor = 1.0;
auto out = ImageType::create (corrected, header);
Header header_broadcast (field);
header_broadcast.ndim() = 4;
header_broadcast.size(3) = in.ndim() > 3 ? in.size(3) : 1;
ReplicatorType field_broadcast (field, header_broadcast);
Scaler scaler = { balance_factor };
ThreadedLoop (in).run (scaler, in, out, field_broadcast);
}
void run ()
{
if (argument.size() % 2)
throw Exception ("The number of arguments must be even, provided as pairs of each input and its corresponding output file.");
if (argument.size() == 2)
WARN("Only one contrast provided. If multi-tissue CSD was performed, provide all components to mtnormalise.");
const int order = get_option_value<int> ("order", DEFAULT_POLY_ORDER);
const float reference_value = get_option_value ("reference", DEFAULT_REFERENCE_VALUE);
const float log_ref_value = std::log (reference_value);
size_t max_iter = DEFAULT_MAIN_ITER_VALUE;
size_t max_balance_iter = DEFAULT_BALANCE_MAXITER_VALUE;
auto opt = get_options ("niter");
if (opt.size()) {
vector<size_t> num = parse_ints<size_t> (opt[0][0]);
if (num.size() < 1 && num.size() > 2)
throw Exception ("unexpected number of entries provided to option \"-niter\"");
for (auto n : num)
if (!n)
throw Exception ("number of iterations must be nonzero");
max_iter = num[0];
if (num.size() > 1)
max_balance_iter = num[1];
}
// Setting the n_tissue_types
const size_t n_tissue_types = argument.size()/2;
size_t num_voxels;
auto index = index_mask_voxels (num_voxels);
Eigen::MatrixXd data (num_voxels, n_tissue_types);
for (size_t n = 0; n < n_tissue_types; ++n) {
if (Path::exists (argument[2*n+1]) && !App::overwrite_files)
throw Exception ("Output file \"" + argument[2*n+1] + "\" already exists. (use -force option to force overwrite)");
load_data (data, argument[2*n], index);
}
size_t num_non_finite = (!data.array().isFinite()).count();
if (num_non_finite > 0) {
WARN ("Input data contain " + str(num_non_finite) + " non-finite voxel" + ( num_non_finite > 1 ? "s" : "" ));
WARN (" Results may be affected if the data contain many non-finite values");
WARN (" Please refine your mask to avoid non-finite values if this is a problem");
}
auto basis = initialise_basis (index, num_voxels, order);
struct finite_and_positive { NOMEMALIGN double operator() (double v) const { return std::isfinite(v) && v > 0.0; } };
Eigen::VectorXd weights = data.rowwise().sum().unaryExpr (finite_and_positive());
Eigen::VectorXd field = Eigen::VectorXd::Ones (num_voxels);
Eigen::VectorXd field_coeffs (basis.cols());
Eigen::VectorXd balance_factors (Eigen::VectorXd::Ones (n_tissue_types));
{
size_t iter = 0;
ProgressBar progress ("performing log-domain intensity normalisation", max_iter);
size_t outliers_changed = detect_outliers (3.0, data, field, balance_factors, weights);
while (++iter <= max_iter) {
INFO ("Iteration: " + str(iter));
size_t balance_iter = 1;
// Iteratively compute tissue balance factors with outlier rejection
do {
DEBUG ("Balance and outlier rejection iteration " + str(balance_iter) + " starts.");
if (n_tissue_types > 1) {
compute_balance_factors (data, field, weights, balance_factors);
INFO (" balance factors (" + str(balance_iter) + "): " + str(balance_factors.transpose()));
}
outliers_changed = detect_outliers (1.5, data, field, balance_factors, weights);
} while (outliers_changed && balance_iter++ < max_balance_iter);
update_field (log_ref_value, basis, data, balance_factors, weights, field_coeffs, field);
progress++;
}
}
auto full_field = compute_full_field (order, field_coeffs, index);
opt = get_options ("check_norm");
if (opt.size()) {
auto out = ImageType::create (opt[0][0], full_field);
threaded_copy (full_field, out);
}
opt = get_options ("check_mask");
if (opt.size())
write_weights (weights, index, opt[0][0]);
opt = get_options ("check_factors");
if (opt.size()) {
File::OFStream factors_output (opt[0][0]);
factors_output << balance_factors.transpose() << "\n";
}
double lognorm_scale = std::exp ((field.array().log() * weights.array()).sum() / weights.sum());
const bool output_balanced = get_options("balanced").size();
for (size_t n = 0; n < n_tissue_types; ++n)
write_output (argument[2*n], argument[2*n+1], output_balanced, balance_factors[n], full_field, lognorm_scale);
}
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