Generating synthetic tau-PET scans in Alzheimer’s disease from MRI, blood biomarkers and demographics with deep learning
The 7 matches
- [1] § Methods › Model development and training › U-Net blocks ↔ src/models/unet3d.py, lines 158–183 · score 0.73 · transposed convolutions, decoder blocks, deeper, stride, upsampling, connection
- [2] § Methods › Participants ↔ notebooks/tau_load_plots.ipynb, lines 19–52 · score 0.70 · PREVENT AD, BACS, LLCF, LZAX, OASIS, UCSF
- [3] § Methods › Model development and training › U-Net architecture ↔ src/models/unet3d.py, lines 158–183 · score 0.64 · skip connections, decoder block, upsamples, layers, convolutional, encoder
- [4] § Methods › Model development and training › Loss function ↔ src/models/loss.py, lines 7–38 · score 0.61 · masked L1 loss, absolute, error, scalar, voxels, brain
- [5] § Methods › Participants ↔ notebooks/tau_spat_sim_plots.ipynb, lines 20–41 · score 0.60 · Berkeley, LLCF, LZAX, OASIS, UCSF, subset
- [6] § Methods › Training ↔ src/models/train.py, lines 116–221 · score 0.53 · validation loss, model weights, optimization, batch, training
- [7] § Methods › Model development and training › Loss function ↔ src/models/train.py, lines 12–68 · score 0.50 · masked L1 loss, scalar, brain, weight, predicted, model
Paper
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The authors' code
Python · 318 lines · 9 KB · CC-BY-NC-4.0 · 2 matches
- """
- 3D U-Net architecture for synthetic tau-PET generation.
- """
- import numpy as np
- import tensorflow as tf
- from keras import Model
- from keras.layers import (
- Activation,
- BatchNormalization,
- Conv3D,
- Conv3DTranspose,
- Cropping3D,
- Dense,
- Input,
- LeakyReLU,
- MaxPooling3D,
- Reshape,
- ZeroPadding3D,
- add,
- concatenate,
- )
- def conv_block(inputs, num_filters, kernel_size=(3, 3, 3), activation=None, padding="same"):
- """
- Apply 3D convolution, batch normalization, and activation.
- Parameters
- ----------
- inputs : tf.Tensor
- Input tensor.
- num_filters : int
- Number of convolutional filters.
- kernel_size : tuple of int, optional
- Convolution kernel size. Default is (3, 3, 3).
- activation : keras.layers.Layer or None, optional
- Activation layer. Default is LeakyReLU().
- padding : str, optional
- Padding mode for convolution. Default is "same".
- Returns
- -------
- x : tf.Tensor
- Output tensor after convolution, batch norm, and activation.
- """
- if activation is None:
- activation = LeakyReLU()
- x = Conv3D(num_filters, kernel_size, padding=padding)(inputs)
- x = BatchNormalization(fused=False)(x)
- x = Activation(activation)(x)
- return x
- def residual_block(inputs, num_filters):
- """
- Residual 3D convolutional block with skip connection.
- Two convolutions with batch normalization and LeakyReLU activations,
- with a skip connection adding the input to the output.
- Parameters
- ----------
- inputs : tf.Tensor
- Input tensor with number of channels matching num_filters.
- num_filters : int
- Number of convolutional filters.
- Returns
- -------
- x : tf.Tensor
- Output tensor after residual connection.
- """
- x = Conv3D(num_filters, (3, 3, 3), padding="same")(inputs)
- x = BatchNormalization(fused=False)(x)
- x = Activation(LeakyReLU())(x)
- x = Conv3D(num_filters, (3, 3, 3), padding="same")(x)
- x = BatchNormalization(fused=False)(x)
- x = add([x, inputs])
- x = Activation(LeakyReLU())(x)
- return x
- def attention_block(inputs):
- """
- Self-attention block for spatial features.
- Computes scaled dot-product attention over spatial voxels, designed for
- bottleneck feature maps with small spatial dimensions.
- Parameters
- ----------
- inputs : tf.Tensor
- Input feature map.
- Returns
- -------
- output : tf.Tensor
- Output tensor after attention mechanism and skip connection.
- """
- query = Conv3D(filters=inputs.shape[-1] // 8, kernel_size=1)(inputs)
- key = Conv3D(filters=inputs.shape[-1] // 8, kernel_size=1)(inputs)
- value = Conv3D(filters=inputs.shape[-1], kernel_size=1)(inputs)
- attention_weights = tf.nn.softmax(tf.matmul(query, key, transpose_b=True) / tf.sqrt(tf.cast(inputs.shape[-1] // 8, dtype=tf.float32)))
- output = tf.matmul(attention_weights, value)
- output = add([output, inputs])
- return output
- def down_block(inputs, num_filters):
- """
- Encoder block combining convolution and residual connection.
- Parameters
- ----------
- inputs : tf.Tensor
- Input tensor.
- num_filters : int
- Number of convolutional filters.
- Returns
- -------
- x : tf.Tensor
- Output tensor after conv and residual blocks.
- """
- x = conv_block(inputs, num_filters)
- x = residual_block(x, num_filters)
- return x
- def bottleneck_block(inputs, num_filters):
- """
- Bottleneck block with attention.
- Parameters
- ----------
- inputs : tf.Tensor
- Input tensor.
- num_filters : int
- Number of convolutional filters.
- Returns
- -------
- x : tf.Tensor
- Output tensor after conv, attention, and conv blocks.
- """
- x = conv_block(inputs, num_filters)
- x = attention_block(x)
- x = conv_block(x, num_filters)
- return x
- def up_block(inputs, skip_connection, num_filters):
- """
- Decoder block with transposed convolution and skip connection.
- Applies transposed convolution to upsample, concatenates with skip connection,
- and applies conv and residual blocks.
- Parameters
- ----------
- inputs : tf.Tensor
- Input tensor (features from deeper layer).
- skip_connection : tf.Tensor
- Encoder feature map from corresponding down_block.
- num_filters : int
- Number of convolutional filters.
- Returns
- -------
- x : tf.Tensor
- Output tensor after upsampling, concatenation, and residual blocks.
- """
- x = Conv3DTranspose(num_filters, (2, 2, 2), strides=(2, 2, 2), padding="same")(inputs)
- x = concatenate([x, skip_connection], axis=4)
- x = conv_block(x, num_filters)
- x = residual_block(x, num_filters)
- return x
- def covariate_bottleneck_layer(covariate_input, spatial_shape=(4, 4, 4), hidden_units=1024, name="covariate"):
- """
- Project scalar covariates into a 3D spatial feature map.
- Passes the input through dense layers and reshapes the output to match
- the specified spatial dimensions for concatenation with CNN features.
- Parameters
- ----------
- covariate_input : tf.Tensor, shape (batch, 1)
- Scalar covariate value (e.g., plasma, age).
- spatial_shape : tuple of int, optional
- Spatial dimensions of the output feature map. Default is (4, 4, 4).
- hidden_units : int, optional
- Number of units in the hidden dense layer. Default is 1024.
- name : str, optional
- Name prefix for the layers. Default is "covariate".
- Returns
- -------
- x : tf.Tensor, shape (batch, *spatial_shape, 1)
- Reshaped feature map ready for concatenation.
- """
- num_voxels = int(np.prod(spatial_shape))
- if name == "plasma":
- dense1_name, dense2_name = "data1", "data2"
- elif name == "age":
- dense1_name, dense2_name = "data3", "data4"
- else:
- dense1_name, dense2_name = f"{name}_dense1", f"{name}_dense2"
- x = Dense(hidden_units, activation="relu", name=f"{name}_dense1")(covariate_input)
- x = Dense(num_voxels, activation="relu", name=f"{name}_dense2")(x)
- x = Reshape((*spatial_shape, 1), name=f"{name}_reshape")(x)
- return x
- def build_tau_pet_unet(
- image_shape=(72, 90, 76, 1),
- padding=(28, 19, 26),
- encoder_filters=(32, 64, 128, 256, 512),
- bottleneck_filters=1024,
- covariate_shape=(4, 4, 4),
- output_activation=None,
- verbose=False,
- ):
- """
- Build a multimodal 3D U-Net for synthetic tau-PET generation.
- Constructs a U-Net encoder-decoder architecture with residual and attention
- blocks. Takes MRI and scalar covariates (plasma, age) as inputs and outputs
- synthetic tau-PET images. Covariates are projected into 3D bottleneck features
- and concatenated with CNN features.
- Parameters
- ----------
- image_shape : tuple of int, optional
- Input MRI image shape (H, W, D, channels). Default is (72, 90, 76, 1).
- padding : tuple of int, optional
- Zero padding applied to MRI input (H_pad, W_pad, D_pad). Default is (28, 19, 26).
- encoder_filters : tuple of int, optional
- Number of filters at each encoder level. Default is (32, 64, 128, 256, 512).
- bottleneck_filters : int, optional
- Number of filters in the bottleneck. Default is 1024.
- covariate_shape : tuple of int, optional
- Spatial shape of covariate bottleneck features. Default is (4, 4, 4).
- output_activation : keras.layers.Layer or None, optional
- Output activation layer. Default is LeakyReLU().
- verbose : bool, optional
- If True, print model summary. Default is False.
- Returns
- -------
- model : keras.Model
- Compiled U-Net model with inputs [mri, plasma, age] and output tau-PET.
- """
- if output_activation is None:
- output_activation = LeakyReLU()
- mri_input = Input(shape=image_shape, name="mri_input")
- plasma_input = Input(shape=(1,), name="plasma_input")
- age_input = Input(shape=(1,), name="age_input")
- x = ZeroPadding3D(padding=padding)(mri_input)
- skips = []
- for num_filters in encoder_filters:
- x = down_block(x, num_filters)
- skips.append(x)
- x = MaxPooling3D((2, 2, 2))(x)
- x = bottleneck_block(x, bottleneck_filters)
- plasma_features = covariate_bottleneck_layer(
- plasma_input,
- spatial_shape=covariate_shape,
- hidden_units=bottleneck_filters,
- name="plasma",
- )
- age_features = covariate_bottleneck_layer(
- age_input,
- spatial_shape=covariate_shape,
- hidden_units=bottleneck_filters,
- name="age",
- )
- x = concatenate([x, plasma_features], axis=4)
- x = concatenate([x, age_features], axis=4)
- for skip_connection, num_filters in zip(reversed(skips), reversed(encoder_filters)):
- x = up_block(x, skip_connection, num_filters)
- x = Conv3D(
- 1,
- (1, 1, 1),
- activation=output_activation,
- bias_initializer="zeros",
- )(x)
- output = Cropping3D(cropping=padding)(x)
- model = Model(
- inputs=[mri_input, plasma_input, age_input],
- outputs=output,
- name="tau_pet_unet",
- )
- if verbose:
- model.summary()
- return model
unet3d.py at commit 4226694, under CC-BY-NC-4.0 · at the source
Overview
- Clinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden
- Memory Clinic, Skåne University Hospital, Malmö, Sweden
- Centre for Mathematical Sciences, Lund University, Lund, Sweden
- C2N Diagnostics LLC, St Louis, MO, USA
- Pharma Research and Early Development, F Hoffmann-La Roche Ltd., Basel, Switzerland
- Eli Lilly and Company, Indianapolis, Indiana, USA
- Department of Neuroscience, University of California, Berkeley, California,USA
- Centre for Studies in the Prevention of Alzheimer’s Disease, Douglas Mental Health Institute, McGill University, Montreal, QC, Canada
- Department of Neurology, Edward and Pearl Fein Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA
- Department of Radiology and Biomedical Imaging, Edward and Pearl Fein Memory and Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA
- Clinical Memory Research Unit, SciLifeLab, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden
Abstract
Tau protein aggregation in the brain is a hallmark of Alzheimer’s disease (AD). Positron emission tomography (PET) is the only in vivo method to visualize tau pathology and estimate both its burden and regional distribution, but the use of tau-PET is constrained by high cost and limited accessibility. Here, we develop a deep learning model to synthesize tau-PET scans from more accessible data: structural magnetic resonance imaging (MRI), demographics, and when available, blood biomarkers. We included 5,191 participants across the AD continuum or with another neurological disorder from 13 cohorts (mean age 70 years, 51% female) and optimized a 3D U-Net neural network with residual and attention units for this task. In held-out test data, synthetic tau-PET reliably modeled tau burden, with correlations of R=
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 7 matches between paragraphs and lines of code.
DeMONLab-BioFINDER/karlsson_synthetic_taupet
4226694b0d3ca9d15e3a427f1f0bc49d0259a05e, 29 June 2026Availability: 1 check, the latest on 28 September 2026: the link answers
- 28 September 2026: the link answers
22 files
- examples/
evaluate_unet.py , Python, 229 lines - examples/
start_unet.sh , Shell, 14 lines - examples/
train_new_unet.py , Python, 182 lines - notebooks/
example_cases_plots.ipyn , Jupyter, 76 linesb - notebooks/
tau_load_plots.ipynb , Jupyter, 98 lines, 1 match - notebooks/
tau_spat_sim_plots.ipynb , Jupyter, 303 lines, 1 match - pretrained_models/
__init__.py , Python, 1 line - pretrained_models/
unet_taupet_v1/ , Python, 1 line__init__.py - pretrained_models/
unet_taupet_v1/ , Python, 148 linesgenerate_multiple_taupet .py - pretrained_models/
unet_taupet_v1/ , Jupyter, 138 linesgenerate_single_taupet.i pynb - pretrained_models/
unet_taupet_v1/ , Python, 186 linesunet3d_v1.py - src/
__init__.py , Python, 1 line - src/
models/ , Python, 1 line__init__.py - src/
models/ , Python, 38 lines, 1 matchloss.py - src/
models/ , Python, 221 lines, 2 matchestrain.py - src/
models/ , Python, 105 linestraining_visualization.p y - src/
models/ , Python, 318 lines, 2 matchesunet3d.py - src/
utils/ , Python, 1 line__init__.py - src/
utils/ , Python, 307 linesimage_helpers.py - src/
utils/ , Python, 48 linesplot_helpers.py - LICENSE, License, 358 lines
- README.md, Text, 125 lines
Code availability
The code and model will be made available at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 20 scripts, each with its path and the digest of its content;
- 7 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
No dataset and no data link were found in the paper.
Data availability
Participant data from open access cohorts (ADNI, A4, OASIS and PREVENT-AD) can be obtained from http://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 2, 28 September 2026
- Language: n/a → en
- Authors: added Renaud La Joie (0000-0003-2581-8100); removed Renaud La Joie
- Funding: added Michael J. Fox Foundation for Parkinson's Research: MJFF‐025507, 2022-Projekt0107; Alzheimer's Association: ZEN24-1069572, SG-23-1061717; Eli Lilly and Company; Cure Alzheimer's Fund; Australian Government: 2022-Projekt0107, 2022-Projekt0080; GHR Foundation: 2022-00775; Lunds Universitet: AF-980907; Knut och Alice Wallenbergs Stiftelse: KAW 2020.0239, (2022-0231), 2022-Projekt0080, 2022-00775, AF-980907, 2022-1259, FO2021-0293, 2020-O000028, 1412/22, 2020.0239; Vetenskapsrådet: ERAPERMED2021-184, 2024-03642, 2022-00775, 2022-Projekt0080, FO2021-0293, AF-980907, 2018, 1412/22, 2018-02052, 2021-02219, 2020-O000028, 2022-1259; Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse: 2020-O000028, WASP/DDLS22-066; Science for Life Laboratory: KAW 2020.0239; Skånes universitetssjukhus: 2022-1259, 2020-O000028, 2022-Projekt0080; Stiftelsen Bundy Academy; University of California, San Francisco; Parkinsonfonden: 1412/22
Version 1, 28 September 2026: the first record
Recorded: type, journal, dates, 23 authors, 72 references.
Cite
This paper
Karlsson, L., Strandberg, O., Smith, R., Tang, W., Arvidsson, I., Åström, K., Hauer, K. O., Janelidze, S., Stomrud, E., Palmqvist, S., Verghese, P. B., Braunstein, J. B., Alzheimer’s Disease Neuroimaging Initiative, PREVENT-AD Research Group, Klein, G., Shcherbinin, S., Jagust, W. J., Villeneuve, S., La Joie, R., . . . Hansson, O. (2026). Generating synthetic tau-PET scans in Alzheimer’s disease from MRI, blood biomarkers and demographics with deep learning. medRxiv (preprint). https://
BibTeX
@article{karlsson2026gen
author = {Karlsson, Linda and Strandberg, Olof and Smith, Ruben and Tang, Weizhong and Arvidsson, Ida and Åström, Kalle and Hauer, Kevin Oliveira and Janelidze, Shorena and Stomrud, Erik and Palmqvist, Sebastian and Verghese, Philip B. and Braunstein, Joel B. and {Alzheimer’s Disease Neuroimaging Initiative} and {PREVENT-AD Research Group} and Klein, Gregory and Shcherbinin, Sergey and Jagust, William J. and Villeneuve, Sylvia and La Joie, Renaud and Rabinovici, Gil D. and Mattsson-Carlgren, Niklas and Vogel, Jacob W. and Hansson, Oskar},
title = {{Generating synthetic tau-PET scans in Alzheimer’s disease from MRI, blood biomarkers and demographics with deep learning}},
journal = {medRxiv (preprint)},
year = {2026},
month = may,
publisher = {medRxiv},
doi = {10.64898/
url = {https://
}
RIS
TY - JOUR
AU - Karlsson, Linda
AU - Strandberg, Olof
AU - Smith, Ruben
AU - Tang, Weizhong
AU - Arvidsson, Ida
AU - Åström, Kalle
AU - Hauer, Kevin Oliveira
AU - Janelidze, Shorena
AU - Stomrud, Erik
AU - Palmqvist, Sebastian
AU - Verghese, Philip B.
AU - Braunstein, Joel B.
AU - Alzheimer’s Disease Neuroimaging Initiative
AU - PREVENT-AD Research Group
AU - Klein, Gregory
AU - Shcherbinin, Sergey
AU - Jagust, William J.
AU - Villeneuve, Sylvia
AU - La Joie, Renaud
AU - Rabinovici, Gil D.
AU - Mattsson-Carlgren, Niklas
AU - Vogel, Jacob W.
AU - Hansson, Oskar
TI - Generating synthetic tau-PET scans in Alzheimer’s disease from MRI, blood biomarkers and demographics with deep learning
T2 - medRxiv (preprint)
J2 - medRxiv
PY - 2026
DA - 2026/
PB - medRxiv
DO - 10.64898/
UR - https://
LA - en
ER -
CSL-JSON
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