A review of machine learning applications for the proton MR spectroscopy workflow

This literature review presents a comprehensive overview of machine learning (ML) applications in proton MR spectroscopy (MRS). As the use of ML techniques in MRS continues to grow, this review aims to provide the MRS community with a structured overview of the state-of-the-art methods. Specifically, we examine and summarize studies published between 2017 and 2023 from major journals in the MR field. We categorize these studies based on a typical MRS workflow, including data acquisition, processing, analysis, and artificial data generation. Our review reveals that ML in MRS is still in its early stages, with a primary focus on processing and analysis techniques, and less attention given to data acquisition. We also found that many studies use similar model architectures, with little comparison to alternative architectures. Additionally, the generation of artificial data is a crucial topic, with no consistent method for its generation. Furthermore, many studies demonstrate that artificial data suffers from generalization issues when tested on in vivo data. We also conclude that risks related to ML models should be addressed, particularly for clinical applications. Therefore, output uncertainty measures and model biases are critical to investigate. Nonetheless, the rapid development of ML in MRS and the promising results from the reviewed studies justify further research in this field.</p

Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence

The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum samples of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired samples of patients with stage III that progressed to stage IV disease (n = 64) was used to identify markers associated with higher tumor burden. Baseline patient samples from the OpACIN-neo study (n = 83) and PRADO study (n = 49; NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. Significance: LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up

Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence

UNLABELLED: The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared with stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum samples of cohorts of patients with melanoma were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired samples of patients with stage III that progressed to stage IV disease (n = 64) was used to identify markers associated with higher tumor burden. Baseline patient samples from the OpACIN-neo study (n = 83) and PRADO study (n = 49; NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially nonresponder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared with 83% for nonresponders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB. SIGNIFICANCE: LRG1 could serve as a potential target and as a biomarker to identify patients with high risk for disease recurrence, and consequently benefit from additional therapies and intensive follow-up

Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have unexpectedly fast input-output properties: Rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na+) and potassium (K+) currents in human pyramidal neurons can explain their fast input-output properties. Human Na+ and K+ currents exhibited more depolarized voltage dependence, slower inactivation, and faster recovery from inactivation compared with their mouse counterparts. Computational modeling showed that despite lower Na+ channel densities in human neurons, the biophysical properties of Na+ channels resulted in higher channel availability and contributed to fast AP kinetics stability. Last, human Na+ channel properties also resulted in a larger dynamic range for encoding of subthreshold membrane potential changes. Thus, biophysical adaptations of voltage-gated Na+ and K+ channels enable fast input-output properties of large human pyramidal neurons

Acoustic fMRI noise:Linear time-invariant system model

Functional magnetic resonance imaging (fMRI) enables sites of brain activation to be localized in human subjects. For auditory system studies, however, the acoustic noise generated by the scanner tends to interfere with the assessments of this activation. Understanding and modeling fMRI acoustic noise is a useful step to its reduction. To study acoustic noise, the MR scanner is modeled as a linear electroacoustical system generating sound pressure signals proportional to the time derivative of the input gradient currents. The transfer function of one MR scanner is determined for two different input specifications: 1) by using the gradient waveform calculated by the scanner software and 2) by using a recording of the gradient current. Up to 4 kHz, the first method is shown as reliable as the second one, and its use is encouraged when direct measurements of gradient currents are not possible. Additionally, the linear order and average damping properties of the gradient coil system are determined by impulse response analysis. Since fMRI is often based on echo planar imaging (EPI) sequences, a useful validation of the transfer function prediction ability can be obtained by calculating the acoustic output for the EPI sequence. We found a predicted sound pressure level (SPL) for the EPI sequence of 104 dB SPL compared to a measured value of 102 dB SPL. As yet, the predicted EPI pressure waveform shows similarity as well as some differences with the directly measured EPI pressure waveform

Time-encoded golden angle radial arterial spin labeling: simultaneous acquisition of angiography and perfusion data

The goal of the current study was to combine a time-encoded pseudo-continuous arterial spin labeling (te-pCASL) scheme with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset both in a very flexible single-slice approach as well as within a multi-slice setting. A te-pCASL labeling preparation and the golden angle radial readout were both used as a temporal resolution tool to retrospectively choose the temporal window for the reconstruction of both angiography and perfusion images from a single-slice dataset. The temporal window could be chosen retrospectively and adjusted to the hemodynamics of the volunteer on the scanner for the single-slice dataset. Angiographic images were reconstructed at a minimum temporal resolution of 69 ms. For the perfusion phase only the densely sampled center of k-space was included in the reconstruction. For a multi-slice acquisition, the golden angle radial readout allowed reconstruction of images with different spatial resolutions to provide angiographic and perfusion information over 10 slices. The te-pCASL preparation was used as the only source for dynamic information. The multi-slice acquisition shows the ability of the golden angle radial readout to display the inflow of the labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage. By combining a te-pCASL preparation with a golden angle radial readout, single-slice high temporal resolution angiography and good quality perfusion images were reconstructed in a flexible manner from a single dataset. Optimizing the golden angle radial readout for reconstructions at multiple spatial resolutions, allows for multi-slice acquisition

Does age at the time of elective cardiac surgery or catheter intervention in children influence the longitudinal development of psychological distress and styles of coping of parents?

To assess the influence of age at a cardiac procedure of children, who underwent elective cardiac surgery or interventional cardiac catheterisation for treatment of congenital cardiac defects between 3 months and 7 years of age, on the longitudinal development of psychological distress and styles of coping of their parents. We used the General Health Questionnaire to measure psychological distress, and the Utrecht Coping List to measure styles of coping. Parents completed questionnaires on average respectively 5 weeks prior to, and 18.7 months after, cardiac surgery or catheter intervention for their child. Apart from one exception, no significant influence was found of the age at which children underwent elective cardiac surgery or catheter intervention on the pre- to postprocedural course of psychological distress and the styles of coping of their parents. Across time, parents of children undergoing surgery reported, on average, significantly higher levels of psychological distress than parents of children who underwent catheter intervention. After the procedure, parents of children who underwent either procedure reported significantly lower levels of psychological distress, and showed a weaker tendency to use several styles of coping, than did their reference groups. Age of the children at the time of elective cardiac surgery or catheter intervention did not influence the course of psychological distress of their parents, nor the styles of coping used by the parents. Future research should investigate in what way the age at which these cardiac procedures are performed influences the emotional and cognitive development of the childre