Publications by authors named "Ekaterina Mikhaylova"

7 Publications

  • Page 1 of 1

Quantification of NG2-positivity for the precise prediction of KMT2A gene rearrangements in childhood acute leukemia.

Genes Chromosomes Cancer 2021 Feb 20;60(2):88-99. Epub 2020 Nov 20.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

It has long been known that there is a link between neuron glial antigen 2 (NG2) surface expression and KMT2A gene rearrangements in acute leukemia (AL). However, the exact levels of NG2 positivity that predict the presence of KMT2A rearrangement are not known. The current study focuses on a cohort of 505 pediatric AL patients who showed any level of positive NG2 expression (greater than 1% of cells) for whom comprehensive genetic data were available. NG2 expression was measured as either the percentage of positive cells or the number of molecules on the cell surface. KMT2A gene rearrangements were identified by FISH. The fusion partner was detected with RT-PCR, LDI-PCR or anchored multiplex PCR followed by high-throughput sequencing. KMT2A-positive samples comprised a substantial proportion of the NG2-positive cohort (180 of 505, 36%), with a total of 19 different types of translocation. Despite its occurrence in other AL genetic subgroups, NG2 expression was significantly increased in AL patients with KMT2A rearrangements in terms of both the cell percentage and number of molecules per cell. The threshold levels (TL) for NG2-positivity were established by ROC analysis of the whole cohort and separately for children less than 1 years old and older with lymphoblastic (ALL) and myeloid (AML) leukemia. The lowest TL was defined in infants with ALL (7%), while in older children, the threshold was higher (12%). In AML patients, the situation was reversed, with 28% NG2-positivity in infants and 14% in patients >1 year old. The defined TLs resulted in improved diagnostic performance compared to the conventional thresholds of 10% and 20% for all patient groups.
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http://dx.doi.org/10.1002/gcc.22915DOI Listing
February 2021

The reduction of Lu background in Lu-based PET scanners using optimized classification.

Phys Med Biol 2020 08 27;65(17):175016. Epub 2020 Aug 27.

Department of Biomedical Engineering, University of California, Davis, CA, United States of America. Author to whom any correspondence should be addressed.

Positron emission tomography (PET) using scanners incorporating lutetium-based (Lu-based) scintillators are widely used in nuclear medicine. However their application in imaging very low (<100 kBq) activity distributions is quite limited due to the intrinsic Lu radiation emitted from the scintillators. To visualize very low activities, Lu background needs to be reduced or removed. This study proposes a classification method to select background coincidences from true coincidences arising from the source by supervised learning using the optimal classifier as determined by investigating 5 different classifiers: logistic regression, support vector machine, random forest, extreme gradient boosting (XGBoost) and deep neural network. Five energy and time-of-flight (TOF) related features from each coincidence event are extracted to form the training and test set in the classification. The proposed method was verified on a pair of TOF-PET detector modules. Since the measured source coincidences cannot be differentiated from the background events experimentally, simulated source coincidences are used to train the classification model. The simulated feature spectra are therefore compared with those obtained from measurement to verify the feasibility of classifying measured coincidences using a model learned by simulation. XGBoost classifier performed most effectively in classifying the coincidences and provided impressively high classification accuracy (>99%). It was subsequently tested by imaging point-like source, planar Derenzo and bar phantoms with the pair of TOF-PET detectors. An 89.4% image contrast enhancement for the Derenzo phantom at an activity concentration of 100 Bq mm, and a 52.4% peak-to-valley ratio improvement across the area of bar phantom at a concentration of 25 Bq mm, were observed on the reconstructed images with XGBoost classification applied. The proposed method could extend the usage of Lu-based PET scanners to very low activity detection and imaging and has the potential to be used in a variety of molecular imaging tasks to detect low-level signals.
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http://dx.doi.org/10.1088/1361-6560/aba088DOI Listing
August 2020

Prototype Small-Animal PET-CT Imaging System for Image-guided Radiation Therapy.

IEEE Access 2019 30;7:143207-143216. Epub 2019 Sep 30.

Department of Radiation Oncology, City of Hope, Duarte, CA 91010, USA.

Molecular imaging is becoming essential for precision targeted radiation therapy, yet progress is hindered from a lack of integrated imaging and treatment systems. We report the development of a prototype positron emission tomography (PET) scanner integrated into a commercial cone beam computed tomography (CBCT) based small animal irradiation system for molecular-image-guided, targeted external beam radiation therapy. The PET component consists of two rotating Hamamatsu time-of-flight PET modules positioned with a bore diameter of 101.6 mm and a radial field-of-view of 53.1 mm. The measured energy resolution after linearity correction at 511 KeV was 12.9% and the timing resolution was 283.6 ps. The measured spatial resolutions at the field-of-view center and 5 mm off the radial center were 2.6 mm × 2.6 mm × 1.6 mm and 2.6 mm × 2.6 mm × 2.7 mm respectively. F-Fluorodeoxyglucose-based PET imaging of a NEMA NU 4-2008 phantom resolved cylindrical volumes with diameters as small as 3 mm. To validate the system in-vivo, we performed Cu-DOTA-M5A PET and computed tomography (CT) imaging of carcinoembryonic antigen (CEA)-positive colorectal cancer in athymic nude mice and compared the results with a commercially available Siemens Inveon PET/CT system. The prototype PET system performed comparably to the Siemens system for identifying the location, size, and shape of tumors. Regions of heterogeneous Cu-DOTA-M5A uptake were observed. Using Cu-DOTA-M5A PET and CT images, a Monte Carlo-based radiation treatment plan was created to escalate the dose to the Cu-DOTA-M5A-based, highly active, biological target volume while largely sparing the normal tissue. Results demonstrate the feasibility of molecular-image-guided treatment plans using the prototype theranostic system.
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http://dx.doi.org/10.1109/access.2019.2944683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239319PMC
September 2019

Optimization of an ultralow-dose high-resolution pediatric PET scanner design based on monolithic scintillators with dual-sided digital SiPM readout: a simulation study.

Phys Med Biol 2017 Oct 19;62(21):8402-8418. Epub 2017 Oct 19.

Department of Electronics and Information Systems, MEDISIP, Ghent University-iMinds Medical IT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent, Belgium. Department of Biomedical Engineering, University of California-Davis, One Shields Avenue, CA 95616, United States of America.

The goal of this simulation study is the performance evaluation and comparison of six potential designs for a time-of-flight PET scanner for pediatric patients of up to about 12 years of age. It is designed to have a high sensitivity and provide high-contrast and high-resolution images. The simulated pediatric PET is a full ring scanner, consisting of 32  ×  32 mm monolithic LYSO:Ce crystals coupled to digital silicon photomultiplier arrays. The six considered designs differ in axial lengths (27.2 cm, 54.4 cm and 102 cm) and crystal thicknesses (22 mm and 11 mm). The simulations are based on measured detector response data. We study two possible detector arrangements: 22 mm-thick crystals with dual-sided readout and 11 mm-thick crystals with back-sided readout. The six designs are simulated by means of the GEANT4 application for tomographic emission software, using the measured spatial, energy and time response of the monolithic scintillator detectors as input. The performance of the six designs is compared on the basis of four studies: (1) spatial resolution; (2) NEMA NU2-2012 sensitivity and scatter fraction (SF) tests; (3) non-prewhitening signal-to-noise ratio observer study; and (4) receiver operating characteristics analysis. Based on the results, two designs are identified as cost-effective solutions for fast and efficient imaging of children: one with 54.4 cm axial field-of-view (FOV) and 22 mm-thick crystals, and another one with 102 cm axial FOV and 11 cm-thick crystals. The first one has a higher center point sensitivity than the second one, but requires dual-sided readout. The second design has the advantage of allowing a whole-body scan in a single bed position acquisition. Both designs have the potential to provide an excellent spatial resolution (∼2 mm) and an ultra-high sensitivity (>100 cps [Formula: see text]).
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http://dx.doi.org/10.1088/1361-6560/aa8eb2DOI Listing
October 2017

Simultaneous reconstruction of attenuation and activity in ToF PET/MRI with additional transmission data.

EJNMMI Phys 2015 Dec;2(Suppl 1):A33

MEDISIP Medical Imaging and Signal Processing Group, Ghent University, IBBT-IBiTech, iMinds Medical IT, Ghent, Belgium.

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http://dx.doi.org/10.1186/2197-7364-2-S1-A33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798680PMC
December 2015

Simulation of the expected performance of a seamless scanner for brain PET based on highly pixelated CdTe detectors.

IEEE Trans Med Imaging 2014 Feb 4;33(2):332-9. Epub 2013 Oct 4.

The aim of this work is the evaluation of the design for a nonconventional PET scanner, the voxel imaging PET (VIP), based on pixelated room-temperature CdTe detectors yielding a true 3-D impact point with a density of 450 channels/cm(3), for a total 6 336 000 channels in a seamless ring shaped volume. The system is simulated and evaluated following the prescriptions of the NEMA NU 2-2001 and the NEMA NU 4-2008 standards. Results show that the excellent energy resolution of the CdTe detectors (1.6% for 511 keV photons), together with the small voxel pitch (1 × 1 × 2 mm(3)), and the crack-free ring geometry, give the design the potential to overcome the current limitations of PET scanners and to approach the intrinsic image resolution limits set by physics. The VIP is expected to reach a competitive sensitivity and a superior signal purity with respect to values commonly quoted for state-of-the-art scintillating crystal PETs. The system can provide 14 cps/kBq with a scatter fraction of 3.95% and 21 cps/kBq with a scatter fraction of 0.73% according to NEMA NU 2-2001 and NEMA NU 4-2008, respectively. The calculated NEC curve has a peak value of 122 kcps at 5.3 kBq/mL for NEMA NU 2-2001 and 908 kcps at 1.6 MBq/mL for NEMA NU 4-2008. The proposed scanner can achieve an image resolution of ~ 1 mm full-width at half-maximum in all directions. The virtually noise-free data sample leads to direct positive impact on the quality of the reconstructed images. As a consequence, high-quality high-resolution images can be obtained with significantly lower number of events compared to conventional scanners. Overall, simulation results suggest the VIP scanner can be operated either at normal dose for fast scanning and high patient throughput, or at low dose to decrease the patient radioactivity exposure. The design evaluation presented in this work is driving the development and the optimization of a fully operative prototype to prove the feasibility of the VIP concept.
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http://dx.doi.org/10.1109/TMI.2013.2284657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003455PMC
February 2014
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