Imaging of Response to Radiosurgery and Immunotherapy in Brain Metastases: Quo Vadis?

Abstract Purpose of Review This review presents an overview of how advanced imaging techniques may help to overcome shortcomings of anatomical MRI for response assessment in patients with brain metastases who are undergoing stereotactic radiosurgery, immunotherapy, or combinations thereof. Recent Findings Study results suggest that parameters derived from amino acid PET, diffusion- and perfusion-weighted MRI, MR spectroscopy, and newer MRI methods are particularly helpful for the evaluation of the response to radiosurgery or checkpoint inhibitor immunotherapy and provide valuable information for the differentiation of radiotherapy-induced changes such as radiation necrosis from brain metastases. The evaluation of these imaging modalities is also of great interest in the light of emerging high-throughput analysis methods such as radiomics, which allow the acquisition of additional data at a low cost. Summary Preliminary results are promising and should be further evaluated. Shortcomings are different levels of PET and MRI standardization, the number of patients enrolled in studies, and the monocentric and retrospective character of most studies.

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Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression

Neuro-Oncology ◽

10.1093/neuonc/noz147 ◽

2019 ◽

Vol 22 (1) ◽

pp. 17-30 ◽

Cited By ~ 12

Author(s):

Norbert Galldiks ◽

Martin Kocher ◽

Garry Ceccon ◽

Jan-Michael Werner ◽

Anna Brunn ◽

...

Keyword(s):

Targeted Therapy ◽

Brain Metastases ◽

Treatment Response ◽

Checkpoint Inhibitors ◽

Imaging Techniques ◽

Additional Information ◽

Contrast Enhanced ◽

Amino Acid Pet ◽

Cancer Types ◽

Induced Changes

Abstract The advent of immunotherapy using immune checkpoint inhibitors (ICIs) and targeted therapy (TT) has dramatically improved the prognosis of various cancer types. However, following ICI therapy or TT—either alone (especially ICI) or in combination with radiotherapy—imaging findings on anatomical contrast-enhanced MRI can be unpredictable and highly variable, and are often difficult to interpret regarding treatment response and outcome. This review aims at summarizing the imaging challenges related to TT and ICI monotherapy as well as combined with radiotherapy in patients with brain metastases, and to give an overview on advanced imaging techniques which potentially overcome some of these imaging challenges. Currently, major evidence suggests that imaging parameters especially derived from amino acid PET, perfusion-/diffusion-weighted MRI, or MR spectroscopy may provide valuable additional information for the differentiation of treatment-induced changes from brain metastases recurrence and the evaluation of treatment response.

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32. TREATMENT MONITORING OF IMMUNOTHERAPY AND TARGETED THERAPY USING AMINO ACID PET IN PATIENTS WITH BRAIN METASTASES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.020 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii5-ii6

Author(s):

Norbert Galldiks ◽

Diana Abdulla ◽

Matthias Scheffler ◽

Fabian Wolpert ◽

Jan-Michael Werner ◽

...

Keyword(s):

Targeted Therapy ◽

Amino Acid ◽

Brain Metastases ◽

Response Assessment ◽

Diagnostic Value ◽

Treatment Monitoring ◽

Fet Pet ◽

Time To Peak ◽

Amino Acid Pet

Abstract PURPOSE Recently, the RANO group has analyzed the additional diagnostic value of amino acid PET in patients with primary and secondary brain tumors and recommended the use of this imaging technique in addition to conventional MRI. Here, we investigated the value of PET using the radiolabled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET) for treatment monitoring of immune checkpoint inhibition (ICI) or targeted therapy (TT) alone or in combination with radiotherapy in patients with brain metastases (BM) since contrast-enhanced MRI often remains inconclusive. METHODS We retrospectively identified 40 patients with 107 BM secondary to melanoma (n=29 with 75 BM) or non-small cell lung cancer (n=11 with 32 BM) treated with ICI or TT who had FET PET (n=60 scans) for treatment monitoring from 2015–2019. The majority of patients (n=37; 92.5%) had radiotherapy during the course of disease. In 27 patients, FET PET was used for the differentiation of treatment-related changes from BM relapse following ICI or TT. In 13 patients, FET PET was performed for response assessment to ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In all lesions, static and dynamic FET PET parameters were obtained (i.e., mean tumour-to-brain ratios (TBR), time-to-peak values). Diagnostic accuracies of PET parameters were evaluated by receiver-operating-characteristic analyses using the clinical follow-up or neuropathological findings as reference. RESULTS A TBR threshold of 1.95 differentiated BM relapse from treatment-related changes with an accuracy of 85% (P=0.003). Metabolic Responders to ICI or TT on FET PET had a significantly longer stable follow-up (threshold of TBR reduction relative to baseline, ≥10%; accuracy, 82%; P=0.004). Furthermore, at follow-up, time-to-peak values in metabolic responders increased significantly (P=0.019). CONCLUSIONS FET PET may add valuable information for treatment monitoring in BM patients treated with ICI or TT.

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POTENTIAL EVALUATION OF YELLOW COTTON (COCHLOSPERMUM REGIUM) PIGMENTS FOR DYE SENSITIZED SOLAR CELLS APPLICATION

10.37516/global.j.sci.eng.2020.008 ◽

2020 ◽

pp. 16-21

Author(s):

PHITCHAPHORN KHAMMEE ◽

YUWALEE UNPAPROM ◽

UBONWAN SUBHASAEN ◽

RAMESHPRABU RAMARAJ

Keyword(s):

Solar Cells ◽

Low Cost ◽

Dye Sensitized Solar Cells ◽

Photoelectric Conversion Efficiency ◽

Photoelectric Conversion ◽

Plant Materials ◽

Natural Pigments ◽

Dye Sensitized ◽

Study Results ◽

Sensitized Solar Cells

Recently, dye-sensitized solar cells (DSSC) have concerned significant attention attributable to their material preparation process, architectural and environmental compatibility, also low cost and effective photoelectric conversion efficiency. Therefore, this study aimed to use potential plant materials for DSSC. This research presents the extraction of natural pigments from yellow cotton flowers (Cochlospermum regium). In addition, the natural pigments were revealed that outstanding advantages, including a wide absorption range (visible light), easy extraction method, safe, innocuous pigments, inexpensive, complete biodegradation and ecofriendly. Methanol was used as a solvent extraction for the yellow cotton flower. The chlorophylls and carotenoid pigments extractions were estimated by a UV-visible spectrometer. The chlorophyll-a, chlorophyll-b, and carotenoid yield were 0.719±0.061 µg/ml, 1.484±0.107 µg/ml and 7.743±0.141 µg/ml, respectively. Thus, this study results suggested that yellow cotton flowers containing reasonable amounts appealable in the DSSC production.

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Mass Spectrometry for Proteomics and Recent Developments in ESI, MALDI and other Ionization Methodologies

Current Proteomics ◽

10.2174/1570164616666190204154653 ◽

2019 ◽

Vol 16 (4) ◽

pp. 267-276

Author(s):

Qurat ul Ain Farooq ◽

Noor ul Haq ◽

Abdul Aziz ◽

Sara Aimen ◽

Muhammad Inam ul Haq

Keyword(s):

Mass Spectrometry ◽

Electrospray Ionization ◽

New Technologies ◽

Protein Complexes ◽

Imaging Techniques ◽

Desorption Electrospray Ionization ◽

High Throughput Analysis ◽

Enhanced Sensitivity ◽

Recent Developments ◽

The Way

Background: Mass spectrometry is a tool used in analytical chemistry to identify components in a chemical compound and it is of tremendous importance in the field of biology for high throughput analysis of biomolecules, among which protein is of great interest. Objective: Advancement in proteomics based on mass spectrometry has led the way to quantify multiple protein complexes, and proteins interactions with DNA/RNA or other chemical compounds which is a breakthrough in the field of bioinformatics. Methods: Many new technologies have been introduced in electrospray ionization (ESI) and Matrixassisted Laser Desorption/Ionization (MALDI) techniques which have enhanced sensitivity, resolution and many other key features for the characterization of proteins. Results: The advent of ambient mass spectrometry and its different versions like Desorption Electrospray Ionization (DESI), DART and ELDI has brought a huge revolution in proteomics research. Different imaging techniques are also introduced in MS to map proteins and other significant biomolecules. These drastic developments have paved the way to analyze large proteins of >200kDa easily. Conclusion: Here, we discuss the recent advancement in mass spectrometry, which is of great importance and it could lead us to further deep analysis of the molecules from different perspectives and further advancement in these techniques will enable us to find better ways for prediction of molecules and their behavioral properties.

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Hyperthermic Intraperitoneal Chemotherapy: A Critical Review

Cancers ◽

10.3390/cancers13133114 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3114

Author(s):

Wim Ceelen ◽

Jesse Demuytere ◽

Ignace de Hingh

Keyword(s):

Intraperitoneal Chemotherapy ◽

Imaging Techniques ◽

Systemic Exposure ◽

Theoretical Concept ◽

Chemotherapeutic Agents ◽

Peritoneal Metastases ◽

Attractive Alternative ◽

True Value ◽

Heated Intraperitoneal Chemotherapy ◽

Study Results

With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal. As a result, the true value of HIPEC in the treatment of peritoneal metastases remains a matter of debate. The current review aims to provide a critical overview of the theoretical concept and preclinical and clinical study results, to outline areas of persisting uncertainty, and to propose a framework to better define the role of HIPEC in the treatment of peritoneal malignancies.

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Correlation of Clinical Parameters with Intracranial Outcome in Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Pd-1/Pd-L1 Inhibitors as Monotherapy

Cancers ◽

10.3390/cancers13071562 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1562

Author(s):

Konstantinos Rounis ◽

Marcus Skribek ◽

Dimitrios Makrakis ◽

Luigi De Petris ◽

Sofia Agelaki ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Disease Progression ◽

Cell Lung Cancer ◽

Response Assessment ◽

Small Cell ◽

University Hospital ◽

Response Analysis ◽

Small Cell Lung

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.

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A generalised approach for high-throughput instance segmentation of stomata in microscope images

Plant Methods ◽

10.1186/s13007-021-00727-4 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Hiranya Jayakody ◽

Paul Petrie ◽

Hugo Jan de Boer ◽

Mark Whitty

Keyword(s):

High Throughput ◽

Imaging Techniques ◽

Detection Algorithm ◽

Input Image ◽

Detection Methods ◽

Sample Collection ◽

High Throughput Analysis ◽

General Applicability ◽

Additional Image ◽

Bounding Boxes

Abstract Background Stomata analysis using microscope imagery provides important insight into plant physiology, health and the surrounding environmental conditions. Plant scientists are now able to conduct automated high-throughput analysis of stomata in microscope data, however, existing detection methods are sensitive to the appearance of stomata in the training images, thereby limiting general applicability. In addition, existing methods only generate bounding-boxes around detected stomata, which require users to implement additional image processing steps to study stomata morphology. In this paper, we develop a fully automated, robust stomata detection algorithm which can also identify individual stomata boundaries regardless of the plant species, sample collection method, imaging technique and magnification level. Results The proposed solution consists of three stages. First, the input image is pre-processed to remove any colour space biases occurring from different sample collection and imaging techniques. Then, a Mask R-CNN is applied to estimate individual stomata boundaries. The feature pyramid network embedded in the Mask R-CNN is utilised to identify stomata at different scales. Finally, a statistical filter is implemented at the Mask R-CNN output to reduce the number of false positive generated by the network. The algorithm was tested using 16 datasets from 12 sources, containing over 60,000 stomata. For the first time in this domain, the proposed solution was tested against 7 microscope datasets never seen by the algorithm to show the generalisability of the solution. Results indicated that the proposed approach can detect stomata with a precision, recall, and F-score of 95.10%, 83.34%, and 88.61%, respectively. A separate test conducted by comparing estimated stomata boundary values with manually measured data showed that the proposed method has an IoU score of 0.70; a 7% improvement over the bounding-box approach. Conclusions The proposed method shows robust performance across multiple microscope image datasets of different quality and scale. This generalised stomata detection algorithm allows plant scientists to conduct stomata analysis whilst eliminating the need to re-label and re-train for each new dataset. The open-source code shared with this project can be directly deployed in Google Colab or any other Tensorflow environment.

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Epidemiology of Secondary Warm Autoimmune Haemolytic Anaemia—A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10061244 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1244

Author(s):

Stinne Tranekær ◽

Dennis Lund Hansen ◽

Henrik Frederiksen

Keyword(s):

Haemolytic Anaemia ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Underlying Disease ◽

Age At Diagnosis ◽

Autoimmune Haemolytic Anaemia ◽

Sex Distribution ◽

Number Of Patients ◽

Study Results ◽

Full Text Review

Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study. Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively. Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.

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Assessment of Lacrimal Duct Patency in Patients Undergoing Endoscopic Medial Maxillectomy

Journal of Clinical Medicine ◽

10.3390/jcm10020245 ◽

2021 ◽

Vol 10 (2) ◽

pp. 245

Author(s):

Andrzej Sieśkiewicz ◽

Tomasz Łysoń ◽

Marek Rogowski ◽

Marek Bielecki ◽

Ewa Gindzienska-Sieskiewicz ◽

...

Keyword(s):

Assessment Method ◽

Test Results ◽

Functional Disorders ◽

Lacrimal Duct ◽

Assessment Tests ◽

Number Of Patients ◽

Study Results ◽

Assessment Techniques ◽

Medial Maxillectomy ◽

Comparison Of The Results

Purpose: The risk of epiphora after medial maxillectomy with lacrimal duct transection is difficult to assess. The data available in the literature are inconclusive due to various operating techniques used by the authors of medical publications, different additional procedures aimed at improving tear drainage after maxillectomy, and a variety of lacrimal duct patency assessment techniques. The aim of our work was to assess the anatomical and functional patency of lacrimal ducts after medial maxillectomy without performing additional procedures to improve tear drainage as well as comparison of the results obtained with different assessment tests. Materials and methods: 21 patients who underwent medial maxillectomy in the years 2016–2019 were assessed for discomfort and epiphora based on patients’ own reports and basic clinical examination, lacrimal duct rinse test, the Munk score, and a modified endoscopic Jones I test. Results: Gradually increasing the sensitivity of the assessment method resulted in an increase in the number of patients with potential tear drainage disorders, starting from 0% in the rinsing test, 4.8% self-reported tearing complaints, 14.3% Munk score, and 19% modified endoscopic Jones I test. Conclusions: The study results revealed that a small fraction of patients tend to report epiphora as a consequence of medial maxillectomy themselves. Subtle functional disorders, which are not particularly bothersome to patients, are more common. More sensitive lacrimal duct patency tests reveal more cases of tear drainage disorders. The results of studies assessing the incidence of epiphora after medial maxillectomy appear to depend on the type of test used.

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Can Agricultural Management Induced Changes in Soil Organic Carbon Be Detected Using Mid-Infrared Spectroscopy?

Remote Sensing ◽

10.3390/rs13122265 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2265

Author(s):

Jonathan Sanderman ◽

Kathleen Savage ◽

Shree Dangal ◽

Gabriel Duran ◽

Charlotte Rivard ◽

...

Keyword(s):

Organic Carbon ◽

Soil Organic Carbon ◽

Soil Carbon ◽

Diffuse Reflectance Spectroscopy ◽

Low Cost ◽

Soil Survey ◽

Mid Infrared ◽

Mir Spectroscopy ◽

Induced Changes ◽

Carbon Change

A major limitation to building credible soil carbon sequestration programs is the cost of measuring soil carbon change. Diffuse reflectance spectroscopy (DRS) is considered a viable low-cost alternative to traditional laboratory analysis of soil organic carbon (SOC). While numerous studies have shown that DRS can produce accurate and precise estimates of SOC across landscapes, whether DRS can detect subtle management induced changes in SOC at a given site has not been resolved. Here, we leverage archived soil samples from seven long-term research trials in the U.S. to test this question using mid infrared (MIR) spectroscopy coupled with the USDA-NRCS Kellogg Soil Survey Laboratory MIR spectral library. Overall, MIR-based estimates of SOC%, with samples scanned on a secondary instrument, were excellent with the root mean square error ranging from 0.10 to 0.33% across the seven sites. In all but two instances, the same statistically significant (p < 0.10) management effect was found using both the lab-based SOC% and MIR estimated SOC% data. Despite some additional uncertainty, primarily in the form of bias, these results suggest that large existing MIR spectral libraries can be operationalized in other laboratories for successful carbon monitoring.

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