Noonan Syndrome (NS) is a rare genetic syndrome typically evident at birth and often linked to early-onset severe heart disease. NS is part of a group of diseases termed RASopathies that are caused by activating mutations of proteins belonging to the Ras and mitogen-activated protein kinase families.
In a new study, researchers at Université de Montréal and CHU Sainte-Justine Research Center show that a MEK inhibitor called trametinib can reverse hypertrophic cardiomyopathy (HCM) and valvular obstruction in patients with RIT1-associated NS.
“Up to this finding, our therapeutic options were limited to surgery, including heart transplant, and symptomatic relief with medication,” said the study’s author, Dr. Gregor Andelfinger, a paediatric cardiologist at CHU Sainte-Justine, a researcher at Sainte-Justine University Hospital Research Center in the fetomaternal and neonatal pathologies axis, and an associate research professor in the pediatrics department of Université de Montréal.
 “Trametinib treatment is the first approach specifically targeted to the molecular cause of RASopathies,” said Dr. Andelfinger. “While our numbers are still very limited, we report the first patients in whom we were not only able to stabilize, but to reverse the disease of the heart. These results pave the way for larger trials, which are now needed.”
Infants less than six months old with NS, HCM and congestive heart failure normally have a poor prognosis, with a one-year survival rate of 34 per cent. In the new study, the Sainte Justine clinical teams used trametinib, an inhibitor targeted specifically against the activating nature of the mutations, to try to treat NS in two patients.
They observed dramatic improvement of clinical and cardiac status in the patients only three months after treatment. Hypertrophy regressed in both patients, with sustained improvement over a total of 17 months of treatment, and normalization of laboratory values. One of the patients, who required ventilation, could be extubated after six weeks of treatment. Both patients showed better overall growth after treatment was started.
"The findings described in this report suggest that a life-threatening form of heart disease affecting young infants might be treatable, which, if true, would be unprecedented and so meaningful for the families whose lives this devastating problem touches,” commented Dr. Bruce Gelb, director of the Mindich Child Health and Development Institute at the Icahn School of Medicine at Mount Sinai,  in New York City.
“Now we need to perform a proper clinical trial to prove that this drug is definitely working for this particular problem," he said.
Santé Montréal https://tinyurl.com/y5xcgh43

A strain in ICU capacity has been linked to adverse patient outcomes. New research suggests that near-simultaneous ICU admissions are frequent and may also have an adverse effect on patient outcomes. Researchers conducted an observational study of patients admitted to an academic adult ICU of a tertiary medical centre. Over the five-year period of the study, they found a correlation between the elapsed time between two consecutive admissions and mortality.
Researchers examined 13,234 consecutive ICU admissions. A quarter of these admissions had an elapsed time between two consecutive admissions of less than 55 minutes. They found a “dose-dependent” and inverse relationship between the elapsed time between admissions and mortality. In summary, the shorter the interval between admissions, the higher the odds of death. Specifically, the adjusted odds ratio (OR) of death gradually decreased by an additional average of 0.93 (95% CI 0.9‒0.97, P=.001) for each log(unit) of time separating admissions.
“This study shows that providing the same level of care during multiple admissions is difficult when patients of equal severity arrive at the same time. Further studies are needed to confirm these findings and work towards ways to improve mechanisms, structures and processes to improve patient outcomes regardless of admission rates,” says Dr. Markos Kashiouris, lead researcher.
CHESThttps://tinyurl.com/y46pl9lf

Recent years have witnessed an explosion in the number of medical images. Growth has been fuelled by technology, regulations and demographic trends. According to one estimate cited by GE , as much as 90 percent of all healthcare data comes from medical imaging.
Technology has made it possible to expect ever-higher resolution imaging, which has directly led to a burgeoning volume of data. Meanwhile, standard-of-care rules require that such imaging be provided across different medical departments and that the data be retained. Finally, there is also the effect of demographics: an ageing population requires more healthcare, and this too has driven demand for more imaging.

Enormous quantum

Digital images are stored in data storage devices after preprocessing. They are transmitted and reprocessed for final applications.
The numbers are impressive. In settings like emergency rooms, imaging per patient can work out to approximately 250 GB of data. Radiologists often examine 200-plus cases a day. A ‘pan scan’ CT of a trauma patient can render 4,000 images.
Given this enormous quantum of digital data provided to an image processor, sophisticated compression techniques have been developed to reduce the size of an image. This reduction is accompanied by a high level of fault tolerance as well as sufficiently good quality of the decoded image at the end of the process.

Medicine’s Holy Grail

Many see machine-assisted analysis of imaging data to be the Holy Grail of medicine, with vital information about organ function and disease states. These, they say, can provide insights not only for the benefit of a single patient but for all victims of a medical condition. For their proponents, gamechanging mathematical tools, in the shape of increasingly sophisticated, quantitative pixel-based analysis, advanced deep learning analytics and artificial intelligence, will pave the way for dramatic advances in the effectiveness of healthcare.
Indeed, there are enough research papers, proofs-of-concept and pilot projects demonstrating how data-based screening algorithms can highlight the subtlest of changes in a nodule or a lesion. Such algorithms learn over time, and become better at what they do, resulting in even greater speed and confidence in the future.

Powering up Big Data

The above processes have been driven by the steady acceleration, over the years, in raw computer processing power. While training an algorithm at the turn of the century took 2-3 months, the same results can now be achieved and iterated within minutes.
Big Data-based pattern analysis has demonstrated the capacity to detect areas of opacities, honeycombing, reticular densities and fibrosis, and thereby provide a list of differentials, using computer aided diagnostic tools. These have been backed up with dynamic contrast enhancement (DCE) texture analysis or 3D multi-planar reconstructions on highly-targeted data subsets, instead of making the time-consuming effort of interrogating and querying a complete imaging dataset.

Data quality and content

In spite of such promise, many problems need to be overcome before medical imaging data can be used to its full potential.
Traditionally, access has been a major barrier. Large healthcare organizations, which generate the bulk of imaging data, tend to keep it siloed in departmental picture archiving and communications systems (PACS).
Analysis is also handicapped by data quality. Medical imaging, as we have mentioned above, covers a gamut of areas from data acquisition and compression, to transmission, enhancement and segmentation.

Denoising and reconstruction

The biggest pre-processing step consists of cleaning up the data by denoising and reconstruction, to eliminate undesirable source signals and highlight the useful ones.
Denoising is a central challenge for all medical imaging modalities, be it ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET).
Typical examples include electronic noise, reverberation artefact with multi-path reflections, and echoes from tissue structures in applications such as blood flow estimation, perfusion or targeted molecular imaging.

Cleaning data in ultrasound

Medical ultrasound offers several advantages over other modalities, such as superior temporal and spatial resolution and the lack of ionising radiation risk. It is also very often more convenient.
Nevertheless, high levels of image artefact prevalence (or ‘clutter’) frequently leads to demand for more expensive modalities, such as magnetic resonance imaging (MRI) or computed tomography (CT). However, (as we shall see), the latter too face their own denoising challenges.
One of the most frequent sources of artefact in ultrasound is off-axis scattering and multi-path reverberation. Clutter from the latter, most pronounced in a patient’s sternum and rib cage, occurs when a reflective tissue structure repeatedly reflects a returning acoustic wave vis-a-vis the ultrasound transducer face.
Such limitations serve to obscure dynamic tissue in regions of interest.

Filtering clutter

There have been two broad approaches to clearing up data clutter in ultrasound. The first consists of classical filters, which operate only in the temporal dimension.
Clutter directly degrades image performance by biasing functional image measurements. Its impact is especially profound in critical areas such as displacement estimation in elastography and blood flow imaging or myocardium strain in cardiac imaging. This impacts adversely on diagnosis of cardiac function through motion tracking or visual inspection of imaging data.
Although efforts continue to be made to improve interpolation from artefact-free regions and modelling to infer heart motion while compensating for image degradation from reverberation artefacts, it is not possible to interpolate abnormal myocardial motion in diseased hearts from statistical models alone. Filtering has therefore been the preferred choice to suppress image artefacts and allow for computing accurate motion tracking from the entire myocardium.
In medical ultrasound, filtering strategies for suppression of clutter have been directed to involve the linear decomposition of received echo signals. This approach seeks to reformulate and express the original data along a new coordinate system, which separates the clutter and signal of interest along different bases. Filtering rejects the clutter, but retains the bases which describe the signal of interest.

SVD: Adding a spatial dimension

Newer techniques add a spatial element to provide a fourdimensional approach (three spatial plus time providing the fourth).
The best example of this is singular value decomposition (SVD), which leverages differences in tissue and blood motion in terms of spatio-temporal coherence. Along with wavelet transform, SVD was developed as one of the most useful linear algebra tools for image compression. SVD is essentially a factorization and iterative approximation technique to reduce any matrix into a smaller invertible and square matrix.
The impact of SVD has been profound, making possible techniques such as ultra-fast ultrasonic imaging, which is based on the unfocused transmission of plane or diverging ultrasound waves. Larger synchronous ultrasound imaging datasets greatly improve the discrimination between tissue and blood motion in Doppler imaging.
SVD has been shown to be far superior to traditional temporal clutter rejection filters, in terms of contrast-to-noise ratio and removal of tissue or probe motion artefacts. Tests have detected completely new microvascular blood flow networks. In the clinical field, this has led to dramatic improvements in the application of high-tech imaging in areas such as the neonate brain.

The case of CT images

CT offers a different set of challenges. Firstly, the process of denoising and reconstruction of CT images depends on statistically-uncertain baseline measurements such as radiation dose. In addition, in spite of huge advancements in acquisition speed, increased signal-to-noise ratio (SNR) and superior image resolution, images are still affected by noise and artefacts.
It is always important (and difficult) to strike a correct balance in the trade-off between reduction in noise on one side, and the conservation of genuine details – such as edges, corners and other structures – in order to maintain or even enhance clinically relevant image content on the other.
Real life choice of methodology poses its own set of challenges, as denoising techniques themselves often provide the means to understand the noise in CT images.
Nevertheless, a variety of algorithm-based techniques have been developed to suppress noise from the CT scanned images. Each has its own merits and demerits. Broadly, these include the use of filters, wavelet decomposition, wave atom transformation, anisotropic diffusion etc. Each produces its own set of metrics to enable comparison, based on key parameters for any imaging modality – MSE (mean square error), SNR and PSNR (peak signal-to-noise ratio), S/MSE (signal to mean square error ratio) and MAD (mean absolute difference).
Practically, interest in denoising CT has also been driven by the recent increase in awareness of radiation-induced cancer. This has made it important to enhance the diagnostic quality of low dose CT, by increasing the signal-to-noise ratio.
There have been several approaches to denoising low-dose CT images. Some researchers have used deep neural networks to improve image quality, based on the use of convolutions with different dilation rates. Compared to standard convolution, this has enabled the image to capture a greater level of contextual information in fewer layers as well as create shortcut connections to transmit information from early layers to later ones.

Approaches in MRI

One of the most prominent methods for denoising MR images has been NLM (non local means). This seeks to reduce noise by exploiting the similarity of image patterns by averaging similar image patterns (typically image patches), and is also used for CT.
Researchers have however developed new approaches. Some of the most exciting use deep learning via feature regression as well as image self-similarity, in order to permit a high degree of automatic denoising. Deep learning in MRI was typically focused on segmentation and classification of reconstructed magnitude images. Its application in lower levels of MRI measurement techniques is more recent and covers a range of processes including image acquisition and signal processing in MR fingerprinting, before denoising and image synthesis.
An intriguing approach to denoising MR images has been proposed by researchers from France’s University of Bordeaux and the Universitat Politecnica de Valencia in Spain.
The method involves a two-stage approach. In the first stage, an over-complete patch-based convolutional neural network blindly removes the noise without specific estimation of the local noise variance to produce a preliminary estimation of the noise-free image. The second stage uses this preliminary denoised image as a guide image within a rotationally invariant non-local means filter to robustly denoise the original noisy image.
The proposed approach has been compared with related state-of-the-art methods and showed competitive results in all the studied cases while being much faster than comparable filters. They present a denoising method that can be blindly applied to any type of MR image since it can automatically deal with both stationary and spatially varying noise patterns.
References

1. https://www.gehealthcare.com/article/beyond-imagingtheparadox-of-ai-and-medical-imaging-innovation
2. https://arxiv.org/ftp/arxiv/papers/1911/1911.04798.pdf

FUJIFILM SonoSite has announced the launch of a strategic relationship with Partners HealthCare to apply artificial intelligence to improve the utility and functionality of portable ultrasound. The two organizations will collaborate to enhance ultrasound technology with AI to enable clinicians to perform scans at the point-of-care, further expanding the accessibility of this technology for clinicians and their patients. The collaboration will be executed through the MGH & BWH Center for Clinical Data Science and leverage the extensive data assets, computational infrastructure and clinical expertise of the Partners HealthCare system.
“Allowing for even greater integration of ultrasound into our healthcare delivery system requires smarter machines,” said Keith Dreyer, DO, PhD, FACR, FSIIM, Chief Data Science Officer, Partners HealthCare. “In emergency settings, the efficiency and cost-effectiveness of portable ultrasound makes is a critical companion to other imaging modalities.”
The first project under the collaboration will target some of the more complex emergency medicine procedures using AI-enabled portable ultrasound. Andrew Liteplo, MD, MGH Department of Emergency Medicine, explains, “If we build scanners that can be used by non-expert users both inside and outside the hospital, we can likely reduce the time delay between trauma and diagnosis, which will translate to more rapid interventions and improved outcomes.”
Diku Mandavia, MD, FACEP, FRCPC, Senior Vice President and Chief Medical Officer of FUJIFILM SonoSite emphasizes, “This collaboration is really focused on embedding AI in portable ultrasound with the goal of providing assistance in 2D image interpretation along with the automation of measurements and calculations – the type of automation that will allow us to increase the accessibility of this critical technology while still delivering high diagnostic value.”
FUJIFILM SonoSite introduced ultrasound systems designed for use at the point of care to the healthcare system over 20 years ago. We have always listened carefully to our customers to ensure their needs are being met and I am proud that we will be able to offer them AI-enhanced technology to expand their utilization of ultrasound, increasing the quality of care they can provide while saving our healthcare system money,” said Rich Fabian, President and Chief Operating Officer of FUJIFILM SonoSite.
Both parties agree that high fidelity, affordable medical imaging could have an impact on a global scale, particularly in the developing world, where access to care is a fundamental challenge. As an important diagnostic tool in the fields of obstetrics and emergency medicine, increased accessibility to, and utilization of, point-of-care ultrasound holds
substantial promise. Through the collaboration, the collective clinical and technical expertise of the organizations will be harnessed to advance the field of point-of-care ultrasound. www.sonosite.com