Near-field coded-mask technique and its potential for proton therapy monitoring.

Objective.Prompt-gamma imaging encompasses several approaches to the online monitoring of the beam range or deposited dose distribution in proton therapy. We test one of the imaging techniques - a coded mask approach - both experimentally and via simulations.Approach.Two imaging setups have been investigated experimentally. Each of them comprised a structured tungsten collimator in the form of a modified uniformly redundant array mask and a LYSO:Ce scintillation detector of fine granularity. The setups differed in detector dimensions and operation mode (1D or 2D imaging). A series of measurements with radioactive sources have been conducted, testing the performance of the setups for near-field gamma imaging. Additionally, Monte Carlo simulations of a larger setup of the same type were conducted, investigating its performance with a realistic gamma source distribution occurring during proton therapy.Main results.The images of point-like sources reconstructed from two small-scale prototypes' data using the maximum-likelihood expectation maximisation algorithm constitute the experimental proof of principle for the near-field coded-mask imaging modality, both in the 1D and the 2D mode. Their precision allowed us to calibrate out certain systematic offsets appearing due to the limited alignment accuracy of setup elements. The simulation of the full-scale setup yielded a mean distal falloff retrieval precision of 0.72 mm in the studies for beam energy range 89.5-107.9 MeV and with 1 × 108protons (a typical number for distal spots). The implemented algorithm of image reconstruction is relatively fast-a typical procedure needs several seconds.Significance.Coded-mask imaging appears a valid option for proton therapy monitoring. The results of simulations let us conclude that the proposed full-scale setup is competitive with the knife-edge-shaped and the multi-parallel slit cameras investigated by other groups.

Carotenoids contribution in rapid diagnosis of multiple sclerosis by Raman spectroscopy.

Rapid and accurate diagnosis of any illness determines the success of treatment. The same applies to multiple sclerosis (MS), chronic, inflammatory, and neurodegenerative diseases (ND) of the central nervous system (CNS). Unfortunately, the definitive diagnosis of MS is prolonged and involves mainly clinical symptoms observation and magnetic resonance imaging (MRI) of the CNS. However, as we previously reported, Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy shed new light on the minimally invasive, label-free, and rapid diagnosis of this illness through blood fraction. Herein we introduce Raman spectroscopy coupled with chemometric analysis to provide more detailed information about the biochemical changes behind MS. This pilot study demonstrates that mentioned combination may provide a new diagnostic biomarker and bring closer to rapid MS diagnosis. It has been shown that Raman spectroscopy provides lipid and carotenoid molecules as useful biomarkers which may be applied for both diagnosis and treatment monitoring.

Characterisation of breast cancer molecular signature and treatment assessment with vibrational spectroscopy and chemometric approach.

Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible.

Spectral signature of multiple sclerosis. Preliminary studies of blood fraction by ATR FTIR technique.

Multiple sclerosis (MS) is a chronic, neurodegenerative disease of central nervous system, characterized by inflammation, demyelination, and gliosis. It is commonly known the rapid and accurate diagnosis of MS determines treatment success. The standard diagnosis contains clinical symptoms observation, magnetic resonance imaging (MRI) of central nervous system (CNS), and analysis of cerebrospinal fluid (CSF). Nonetheless, since CSF sampling is considered invasive and not all individuals are eligible for MRI we have decided to propose other diagnostic tool such as spectroscopy. Unlike lumbar puncture, blood collection is a routine procedure regarded as low-invasive; therefore, we used Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy. This technique was combined with chemometrics and detailed spectral assay to analyse blood plasma and serum samples collected from MS patients and healthy individuals. The results revealed a clear identification pattern of MS, suggesting the conformation changes of amide III collagen-like proteins in plasma and the dominance of amide I ß-sheet structures. Those changes in serum spectra seem to be useful for sample differentiation.

COVID-19: A New Challenge for Pulmonary Rehabilitation?

Coronavirus disease 2019 (COVID-19), currently one of the immense burdens for global healthcare, is often characterized by rapid progression and the occurrence of symptoms particularly affecting the respiratory system. Continuous refinement of treatment protocols improves prognosis; however, COVID-19 survivors are often left with the symptomatic burden of dyspnea and fatigue. Therefore, it is necessary to continue comprehensive treatment including pulmonary rehabilitation. This study aimed to review the available literature on pulmonary rehabilitation in patients diagnosed with COVID-19. The pulmonary rehabilitation programs implemented various forms, i.e., aerobic exercise, breathing exercises, effective cough exercises, diaphragmatic breathing, and respiratory muscle training. Based on the literature review, it was found that pulmonary rehabilitation programs result in an improvement of respiratory function, reduction of fatigue and dyspnea, and improvement in exercise endurance and quality of life after completing both short-term and long-term programs, but depression and anxiety problems did not improve. Pulmonary rehabilitation combined with psychological therapy is crucial for COVID-19 survivors and plays a substantial role in patients' recovery.

Publisher Correction: Classification of aggressive and classic mantle cell lymphomas using synchrotron Fourier Transform Infrared microspectroscopy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Classification of aggressive and classic mantle cell lymphomas using synchrotron Fourier Transform Infrared microspectroscopy.

Mantle cell lymphoma (MCL) is regarded as an incurable neoplasm, even to the novel drug strategies. It is known MCL has two morphological variants- classic and aggressive. Aggressive MCL is characterized by a higher mitotic index and proliferation rate, and poor overall survival in comparison to classic subtype. The insight into the detailed biochemical composition of MCL is crucial in the further development of diagnostic and treatment guidelines for MCL patients; therefore Synchrotron radiation Fourier Transform Infrared (S-FTIR) microspectroscopy combined with Principal Component Analysis (PCA) was used. The major spectral differences were observed in proteins and nucleic acids content, revealing a classification scheme of classic and aggressive MCLs. The results obtained suggest that FTIR microspectroscopy has reflected the histopathological discrimination of both MCL subtypes.

Central Corneal Thickness can be Related to Diabetic Peripheral Neuropathy in Children with Type 1 Diabetes.

AIMS: Diabetic eye disease with its various manifestations as well as diabetic neuropathy may occur in patients with type 1 diabetes (T1D) after several years of diabetes duration. Pachymetry is a promising method evaluating central corneal thickness (CCT) in diabetic patients. The aim of the study was to evaluate the CCT values in children with T1D and its relationship to neurophysiological markers of diabetic neuropathy. METHODS: The study groups included 119 T1D children with average 5.3 years of diabetes duration and 38 age-matched controls. CCT index was measured with pachymeter in all subjects and in 19/119 of T1D patients the CCT values were referred to the ENG-EMG-SSR study results. RESULTS: In T1D patients the higher CCT values were observed as compared to healthy controls (p=0.037). Correlations between CCT values and both distal latency of the motor fibers of the median nerve (R=0.51; p=0.044) and conduction velocity of this nerve (R=-0.55; p=0.027) were noted. A conduction velocity of the sensory fibers of sural nerve correlated negatively with CCT index (R=-0.50; p=0.045) in the T1D patients. CONCLUSIONS: CCT measurement may be helpful in the referral of the asymptomatic pediatric T1D patients to assess an early stage of diabetic neuropathy.

The HD-OCT Study May Be Useful in Searching for Markers of Preclinical Stage of Diabetic Retinopathy in Patients with Type 1 Diabetes.

The aim of the study was to analyze the thickness of individual retinal layers in patients with type 1 diabetes (T1D) in comparison to the control group and in relation to markers of diabetes metabolic control. The study group consisted of 111 patients with an average of 6-years of T1D duration. The control group included 36 gender- and age-matched individuals. In all patients optical coherence tomography (OCT) study was performed using HD-OCT Cirrus 5000 with evaluation of optic nerve head (ONH) parameters, thickness of retinal nerve fiber layer (RNFL) with its quadrants, macular full-thickness parameters, ganglion cells with inner plexus layer (GCIPL) and choroidal thickness (CT). Lower disc area value was observed in the study group as compared to controls (p = 0.0215). Negative correlations were found both between age at examination and rim area (R = -0.28, p = 0.0007) and between superior RNFL thickness and duration of diabetes (R = -0.20, p = 0.0336). Positive correlation between center thickness and SD for average glycemia (R = 0.30, p = 0.0071) was noted. Temporal CT correlated positively with age at examination (R = 0.21, p = 0.0127). The selected parameters the HD-OCT study may in the future serve as potential markers of preclinical phase of DR in patients with T1D.

Interleukin-1 Receptor Antagonist Protects Newborn Mice Against Pulmonary Hypertension.

Pulmonary hypertension secondary to bronchopulmonary dysplasia (BPD-PH) represents a major complication of BPD in extremely preterm infants for which there are currently no safe and effective interventions. The abundance of interleukin-1 (IL-1) is strongly correlated with the severity and long-term outcome of BPD infants and we have previously shown that IL-1 receptor antagonist (IL-1Ra) protects against murine BPD; therefore, we hypothesized that IL-1Ra may also be effective against BPD-PH. We employed daily injections of IL-1Ra in a murine model in which BPD/BPD-PH was induced by antenatal LPS and postnatal hyperoxia of 65% O2. Pups reared in hyperoxia for 28 days exhibited a BPD-PH-like disease accompanied by significant changes in pulmonary vascular morphology: micro-CT revealed an 84% reduction in small vessels (4-5 µm diameter) compared to room air controls; this change was prevented by IL-1Ra. Pulmonary vascular resistance, assessed at day 28 of life by echocardiography using the inversely-related surrogate marker time-to-peak-velocity/right ventricular ejection time (TPV/RVET), increased in hyperoxic mice (0.27 compared to 0.32 in air controls), and fell significantly with daily IL-1Ra treatment (0.31). Importantly, in vivo cine-angiography revealed that this protection afforded by IL-1Ra treatment for 28 days is maintained at day 60 of life. Despite an increased abundance of mediators of pulmonary angiogenesis in day 5 lung lysates, namely vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1), no difference was detected in ex vivo pulmonary vascular reactivity between air and hyperoxia mice as measured in precision cut lung slices, or by immunohistochemistry in alpha-smooth muscle actin (α-SMA) and endothelin receptor type-A (ETA) at day 28. Further, on day 28 of life we observed cardiac fibrosis by Sirius Red staining, which was accompanied by an increase in mRNA expression of galectin-3 and CCL2 (chemokine (C-C motif) ligand 2) in whole hearts of hyperoxic pups, which improved with IL-1Ra. In summary, our findings suggest that daily administration of the anti-inflammatory IL-1Ra prevents the increase in pulmonary vascular resistance and the pulmonary dysangiogenesis of murine BPD-PH, thus pointing to IL-1Ra as a promising candidate for the treatment of both BPD and BPD-PH.

Lung function imaging methods in Cystic Fibrosis pulmonary disease.

Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

FPA-FTIR Microspectroscopy for Monitoring Chemotherapy Efficacy in Triple-Negative Breast Cancer.

Triple-negative breast cancer is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. Approximately 70% of triple-negative breast cancer patients fail to achieve a pathologic complete response (pCR) after chemotherapy due to the lack of targeted therapies for this subtype. We report here the development of a focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopic technique combined with principal component analysis (PCA) for monitoring chemotherapy effects in triple-negative breast cancer patients. The PCA results obtained using the FPA-FTIR spectral data collected from the same patients before and after the chemotherapy revealed discriminatory features that were consistent with the pathologic and clinical responses to chemotherapy, indicating the potential of the technique as a monitoring tool for observing chemotherapy efficacy.