10 research outputs found
A cross-scanner and cross-tracer deep learning method for the recovery of standard-dose imaging quality from low-dose PET
PURPOSE: A critical bottleneck for the credibility of artificial intelligence (AI) is replicating the results in the diversity of clinical practice. We aimed to develop an AI that can be independently applied to recover high-quality imaging from low-dose scans on different scanners and tracers. METHODS: Brain [(18)F]FDG PET imaging of 237 patients scanned with one scanner was used for the development of AI technology. The developed algorithm was then tested on [(18)F]FDG PET images of 45 patients scanned with three different scanners, [(18)F]FET PET images of 18 patients scanned with two different scanners, as well as [(18)F]Florbetapir images of 10 patients. A conditional generative adversarial network (GAN) was customized for cross-scanner and cross-tracer optimization. Three nuclear medicine physicians independently assessed the utility of the results in a clinical setting. RESULTS: The improvement achieved by AI recovery significantly correlated with the baseline image quality indicated by structural similarity index measurement (SSIM) (r = −0.71, p < 0.05) and normalized dose acquisition (r = −0.60, p < 0.05). Our cross-scanner and cross-tracer AI methodology showed utility based on both physical and clinical image assessment (p < 0.05). CONCLUSION: The deep learning development for extensible application on unknown scanners and tracers may improve the trustworthiness and clinical acceptability of AI-based dose reduction. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05644-1
Ea-GANs: Edge-Aware Generative Adversarial Networks for Cross-Modality MR Image Synthesis
Magnetic resonance (MR) imaging is a widely used medical imaging protocol that can be configured to provide different contrasts between the tissues in human body. By setting different scanning parameters, each MR imaging modality reflects the unique visual characteristic of scanned body part, benefiting the subsequent analysis from multiple perspectives. To utilize the complementary information from multiple imaging modalities, cross-modality MR image synthesis has aroused increasing research interest recently. However, most existing methods only focus on minimizing pixel/voxel-wise intensity difference but ignore the textural details of image content structure, which affects the quality of synthesized images. In this paper, we propose edge-aware generative adversarial networks (Ea-GANs) for cross-modality MR image synthesis. Specifically, we integrate edge information, which reflects the textural structure of image content and depicts the boundaries of different objects in images, to reduce this gap. Corresponding to different learning strategies, two frameworks are proposed, i.e., a generator-induced Ea-GAN (gEa-GAN) and a discriminator-induced Ea-GAN (dEa-GAN). The gEa-GAN incorporates the edge information via its generator, while the dEa-GAN further does this from both the generator and the discriminator so that the edge similarity is also adversarially learned. In addition, the proposed Ea-GANs are 3D-based and utilize hierarchical features to capture contextual information. The experimental results demonstrate that the proposed Ea-GANs, especially the dEa-GAN, outperform multiple state-of-the-art methods for cross-modality MR image synthesis in both qualitative and quantitative measures. Moreover, the dEa-GAN also shows excellent generality to generic image synthesis tasks on benchmark datasets about facades, maps, and cityscapes
Full-dose PET Synthesis from Low-dose PET Using High-efficiency Diffusion Denoising Probabilistic Model
To reduce the risks associated with ionizing radiation, a reduction of
radiation exposure in PET imaging is needed. However, this leads to a
detrimental effect on image contrast and quantification. High-quality PET
images synthesized from low-dose data offer a solution to reduce radiation
exposure. We introduce a diffusion-model-based approach for estimating
full-dose PET images from low-dose ones: the PET Consistency Model (PET-CM)
yielding synthetic quality comparable to state-of-the-art diffusion-based
synthesis models, but with greater efficiency. There are two steps: a forward
process that adds Gaussian noise to a full dose PET image at multiple
timesteps, and a reverse diffusion process that employs a PET Shifted-window
Vision Transformer (PET-VIT) network to learn the denoising procedure
conditioned on the corresponding low-dose PETs. In PET-CM, the reverse process
learns a consistency function for direct denoising of Gaussian noise to a clean
full-dose PET. We evaluated the PET-CM in generating full-dose images using
only 1/8 and 1/4 of the standard PET dose. Comparing 1/8 dose to full-dose
images, PET-CM demonstrated impressive performance with normalized mean
absolute error (NMAE) of 1.233+/-0.131%, peak signal-to-noise ratio (PSNR) of
33.915+/-0.933dB, structural similarity index (SSIM) of 0.964+/-0.009, and
normalized cross-correlation (NCC) of 0.968+/-0.011, with an average generation
time of 62 seconds per patient. This is a significant improvement compared to
the state-of-the-art diffusion-based model with PET-CM reaching this result 12x
faster. In the 1/4 dose to full-dose image experiments, PET-CM is also
competitive, achieving an NMAE 1.058+/-0.092%, PSNR of 35.548+/-0.805dB, SSIM
of 0.978+/-0.005, and NCC 0.981+/-0.007 The results indicate promising low-dose
PET image quality improvements for clinical applications
Clinical microbiology with multi-view deep probabilistic models
Clinical microbiology is one of the critical topics of this century. Identification
and discrimination of microorganisms is considered a global public health
threat by the main international health organisations, such as World Health
Organisation (WHO) or the European Centre for Disease Prevention and Control
(ECDC). Rapid spread, high morbidity and mortality, as well as the economic
burden associated with their treatment and control are the main causes of their
impact. Discrimination of microorganisms is crucial for clinical applications, for
instance, Clostridium difficile (C. diff ) increases the mortality and morbidity of
healthcare-related infections. Furthermore, in the past two decades, other bacteria,
including Klebsiella pneumoniae (K. pneumonia), have demonstrated a significant
propensity to acquire antibiotic resistance mechanisms. Consequently, the use of
an ineffective antibiotic may result in mortality. Machine Learning (ML) has the
potential to be applied in the clinical microbiology field to automatise current
methodologies and provide more efficient guided personalised treatments.
However, microbiological data are challenging to exploit owing to the presence
of a heterogeneous mix of data types, such as real-valued high-dimensional data,
categorical indicators, multilabel epidemiological data, binary targets, or even
time-series data representations. This problem, which in the field of ML is known
as multi-view or multi-modal representation learning, has been studied in other
application fields such as mental health monitoring or haematology. Multi-view
learning combines different modalities or views representing the same data to extract
richer insights and improve understanding. Each modality or view corresponds
to a distinct encoding mechanism for the data, and this dissertation specifically
addresses the issue of heterogeneity across multiple views.
In the probabilistic ML field, the exploitation of multi-view learning is also
known as Bayesian Factor Analysis (FA). Current solutions face limitations when
handling high-dimensional data and non-linear associations. Recent research
proposes deep probabilistic methods to learn hierarchical representations of the data,
which can capture intricate non-linear relationships between features. However,
some Deep Learning (DL) techniques rely on complicated representations, which
can hinder the interpretation of the outcomes. In addition, some inference methods
used in DL approaches can be computationally burdensome, which can hinder their
practical application in real-world situations. Therefore, there is a demand for
more interpretable, explainable, and computationally efficient techniques for highdimensional
data. By combining multiple views representing the same information, such as genomic, proteomic, and epidemiologic data, multi-modal representation
learning could provide a better understanding of the microbial world. Hence,
in this dissertation, the development of two deep probabilistic models, that can
handle current limitations in state-of-the-art of clinical microbiology, are proposed.
Moreover, both models are also tested in two real scenarios regarding antibiotic
resistance prediction in K. pneumoniae and automatic ribotyping of C. diff in
collaboration with the Instituto de Investigación Sanitaria Gregorio Marañón
(IISGM) and the Instituto Ramón y Cajal de Investigación Sanitaria (IRyCIS).
The first presented algorithm is the Kernelised Sparse Semi-supervised Heterogeneous
Interbattery Bayesian Analysis (SSHIBA). This algorithm uses a kernelised
formulation to handle non-linear data relationships while providing compact representations
through the automatic selection of relevant vectors. Additionally, it
uses an Automatic Relevance Determination (ARD) over the kernel to determine
the input feature relevance functionality. Then, it is tailored and applied to the
microbiological laboratories of the IISGM and IRyCIS to predict antibiotic resistance
in K. pneumoniae. To do so, specific kernels that handle Matrix-Assisted
Laser Desorption Ionization (MALDI)-Time-Of-Flight (TOF) mass spectrometry
of bacteria are used. Moreover, by exploiting the multi-modal learning between
the spectra and epidemiological information, it outperforms other state-of-the-art
algorithms. Presented results demonstrate the importance of heterogeneous models
that can analyse epidemiological information and can automatically be adjusted for
different data distributions. The implementation of this method in microbiological
laboratories could significantly reduce the time required to obtain resistance results
in 24-72 hours and, moreover, improve patient outcomes.
The second algorithm is a hierarchical Variational AutoEncoder (VAE) for
heterogeneous data using an explainable FA latent space, called FA-VAE. The
FA-VAE model is built on the foundation of the successful KSSHIBA approach for
dealing with semi-supervised heterogeneous multi-view problems. This approach
further expands the range of data domains it can handle. With the ability to
work with a wide range of data types, including multilabel, continuous, binary,
categorical, and even image data, the FA-VAE model offers a versatile and powerful
solution for real-world data sets, depending on the VAE architecture. Additionally,
this model is adapted and used in the microbiological laboratory of IISGM, resulting
in an innovative technique for automatic ribotyping of C. diff, using MALDI-TOF
data. To the best of our knowledge, this is the first demonstration of using any
kind of ML for C. diff ribotyping. Experiments have been conducted on strains
of Hospital General Universitario Gregorio Marañón (HGUGM) to evaluate the
viability of the proposed approach. The results have demonstrated high accuracy
rates where KSSHIBA even achieved perfect accuracy in the first data collection.
These models have also been tested in a real-life outbreak scenario at the HGUGM,
where successful classification of all outbreak samples has been achieved by FAVAE. The presented results have not only shown high accuracy in predicting
each strain’s ribotype but also revealed an explainable latent space. Furthermore,
traditional ribotyping methods, which rely on PCR, required 7 days while FA-VAE
has predicted equal results on the same day. This improvement has significantly
reduced the time response by helping in the decision-making of isolating patients
with hyper-virulent ribotypes of C. diff on the same day of infection. The promising
results, obtained in a real outbreak, have provided a solid foundation for further
advancements in the field. This study has been a crucial stepping stone towards
realising the full potential of MALDI-TOF for bacterial ribotyping and advancing
our ability to tackle bacterial outbreaks.
In conclusion, this doctoral thesis has significantly contributed to the field of
Bayesian FA by addressing its drawbacks in handling various data types through
the creation of novel models, namely KSSHIBA and FA-VAE. Additionally, a
comprehensive analysis of the limitations of automating laboratory procedures in
the microbiology field has been carried out. The shown effectiveness of the newly
developed models has been demonstrated through their successful implementation in
critical problems, such as predicting antibiotic resistance and automating ribotyping.
As a result, KSSHIBA and FA-VAE, both in terms of their technical and practical
contributions, signify noteworthy progress both in the clinical and the Bayesian
statistics fields. This dissertation opens up possibilities for future advancements in
automating microbiological laboratories.La microbiología clínica es uno de los temas críticos de este siglo. La identificación
y discriminación de microorganismos se considera una amenaza mundial
para la salud pública por parte de las principales organizaciones internacionales de
salud, como la Organización Mundial de la Salud (OMS) o el Centro Europeo para
la Prevención y Control de Enfermedades (ECDC). La rápida propagación, alta
morbilidad y mortalidad, así como la carga económica asociada con su tratamiento
y control, son las principales causas de su impacto. La discriminación de microorganismos
es crucial para aplicaciones clínicas, como el caso de Clostridium difficile
(C. diff ), el cual aumenta la mortalidad y morbilidad de las infecciones relacionadas
con la atención médica. Además, en las últimas dos décadas, otros tipos de bacterias,
incluyendo Klebsiella pneumoniae (K. pneumonia), han demostrado una
propensión significativa a adquirir mecanismos de resistencia a los antibióticos. En
consecuencia, el uso de un antibiótico ineficaz puede resultar en un aumento de la
mortalidad. El aprendizaje automático (ML) tiene el potencial de ser aplicado en
el campo de la microbiología clínica para automatizar las metodologías actuales y
proporcionar tratamientos personalizados más eficientes y guiados.
Sin embargo, los datos microbiológicos son difíciles de explotar debido a la
presencia de una mezcla heterogénea de tipos de datos, tales como datos reales de
alta dimensionalidad, indicadores categóricos, datos epidemiológicos multietiqueta,
objetivos binarios o incluso series temporales. Este problema, conocido en el campo
del aprendizaje automático (ML) como aprendizaje multimodal o multivista, ha
sido estudiado en otras áreas de aplicación, como en el monitoreo de la salud mental
o la hematología. El aprendizaje multivista combina diferentes modalidades o vistas
que representan los mismos datos para extraer conocimientos más ricos y mejorar la
comprensión. Cada vista corresponde a un mecanismo de codificación distinto para
los datos, y esta tesis aborda particularmente el problema de la heterogeneidad
multivista.
En el campo del aprendizaje automático probabilístico, la explotación del aprendizaje
multivista también se conoce como Análisis de Factores (FA) Bayesianos.
Las soluciones actuales enfrentan limitaciones al manejar datos de alta dimensionalidad
y correlaciones no lineales. Investigaciones recientes proponen métodos
probabilísticos profundos para aprender representaciones jerárquicas de los datos,
que pueden capturar relaciones no lineales intrincadas entre características. Sin
embargo, algunas técnicas de aprendizaje profundo (DL) se basan en representaciones
complejas, dificultando así la interpretación de los resultados. Además, algunos métodos de inferencia utilizados en DL pueden ser computacionalmente
costosos, obstaculizando su aplicación práctica. Por lo tanto, existe una demanda de
técnicas más interpretables, explicables y computacionalmente eficientes para datos
de alta dimensionalidad. Al combinar múltiples vistas que representan la misma
información, como datos genómicos, proteómicos y epidemiológicos, el aprendizaje
multimodal podría proporcionar una mejor comprensión del mundo microbiano.
Dicho lo cual, en esta tesis se proponen el desarrollo de dos modelos probabilísticos
profundos que pueden manejar las limitaciones actuales en el estado del arte de la
microbiología clínica. Además, ambos modelos también se someten a prueba en
dos escenarios reales relacionados con la predicción de resistencia a los antibióticos
en K. pneumoniae y el ribotipado automático de C. diff en colaboración con el
IISGM y el IRyCIS.
El primer algoritmo presentado es Kernelised Sparse Semi-supervised Heterogeneous
Interbattery Bayesian Analysis (SSHIBA). Este algoritmo utiliza una
formulación kernelizada para manejar correlaciones no lineales proporcionando representaciones
compactas a través de la selección automática de vectores relevantes.
Además, utiliza un Automatic Relevance Determination (ARD) sobre el kernel
para determinar la relevancia de las características de entrada. Luego, se adapta
y aplica a los laboratorios microbiológicos del IISGM y IRyCIS para predecir la
resistencia a antibióticos en K. pneumoniae. Para ello, se utilizan kernels específicos
que manejan la espectrometría de masas Matrix-Assisted Laser Desorption
Ionization (MALDI)-Time-Of-Flight (TOF) de bacterias. Además, al aprovechar el
aprendizaje multimodal entre los espectros y la información epidemiológica, supera
a otros algoritmos de última generación. Los resultados presentados demuestran la
importancia de los modelos heterogéneos ya que pueden analizar la información
epidemiológica y ajustarse automáticamente para diferentes distribuciones de datos.
La implementación de este método en laboratorios microbiológicos podría reducir
significativamente el tiempo requerido para obtener resultados de resistencia en
24-72 horas y, además, mejorar los resultados para los pacientes.
El segundo algoritmo es un modelo jerárquico de Variational AutoEncoder
(VAE) para datos heterogéneos que utiliza un espacio latente con un FA explicativo,
llamado FA-VAE. El modelo FA-VAE se construye sobre la base del enfoque de
KSSHIBA para tratar problemas semi-supervisados multivista. Esta propuesta
amplía aún más el rango de dominios que puede manejar incluyendo multietiqueta,
continuos, binarios, categóricos e incluso imágenes. De esta forma, el modelo
FA-VAE ofrece una solución versátil y potente para conjuntos de datos realistas,
dependiendo de la arquitectura del VAE. Además, este modelo es adaptado y
utilizado en el laboratorio microbiológico del IISGM, lo que resulta en una técnica
innovadora para el ribotipado automático de C. diff utilizando datos MALDI-TOF.
Hasta donde sabemos, esta es la primera demostración del uso de cualquier tipo
de ML para el ribotipado de C. diff. Se han realizado experimentos en cepas del Hospital General Universitario Gregorio Marañón (HGUGM) para evaluar la
viabilidad de la técnica propuesta. Los resultados han demostrado altas tasas de
precisión donde KSSHIBA incluso logró una clasificación perfecta en la primera
colección de datos. Estos modelos también se han probado en un brote real
en el HGUGM, donde FA-VAE logró clasificar con éxito todas las muestras del
mismo. Los resultados presentados no solo han demostrado una alta precisión
en la predicción del ribotipo de cada cepa, sino que también han revelado un
espacio latente explicativo. Además, los métodos tradicionales de ribotipado, que
dependen de PCR, requieren 7 días para obtener resultados mientras que FA-VAE
ha predicho resultados correctos el mismo día del brote. Esta mejora ha reducido
significativamente el tiempo de respuesta ayudando así en la toma de decisiones
para aislar a los pacientes con ribotipos hipervirulentos de C. diff el mismo día
de la infección. Los resultados prometedores, obtenidos en un brote real, han
sentado las bases para nuevos avances en el campo. Este estudio ha sido un paso
crucial hacia el despliegue del pleno potencial de MALDI-TOF para el ribotipado
bacteriana avanzado así nuestra capacidad para abordar brotes bacterianos.
En conclusión, esta tesis doctoral ha contribuido significativamente al campo
del FA Bayesiano al abordar sus limitaciones en el manejo de tipos de datos
heterogéneos a través de la creación de modelos noveles, concretamente, KSSHIBA
y FA-VAE. Además, se ha llevado a cabo un análisis exhaustivo de las limitaciones de
la automatización de procedimientos de laboratorio en el campo de la microbiología.
La efectividad de los nuevos modelos, en este campo, se ha demostrado a través de su
implementación exitosa en problemas críticos, como la predicción de resistencia a los
antibióticos y la automatización del ribotipado. Como resultado, KSSHIBA y FAVAE,
tanto en términos de sus contribuciones técnicas como prácticas, representan
un progreso notable tanto en los campos clínicos como en la estadística Bayesiana.
Esta disertación abre posibilidades para futuros avances en la automatización de
laboratorios microbiológicos.Programa de Doctorado en Multimedia y Comunicaciones por la Universidad Carlos III de Madrid y la Universidad Rey Juan CarlosPresidente: Juan José Murillo Fuentes.- Secretario: Jerónimo Arenas García.- Vocal: María de las Mercedes Marín Arriaz