Publications by authors named "Keiichi Nakagawa"

253 Publications

A retrospective analysis of radiotherapy in the treatment of external auditory canal carcinoma.

Mol Clin Oncol 2021 Mar 13;14(3):45. Epub 2021 Jan 13.

Department of Radiology, The University of Tokyo Hospital, Bunkyo-ku, Tokyo 113-8655, Japan.

External auditory canal carcinoma (EACC) is a rare disease. The current study aimed to evaluate the clinical outcomes of patients treated with external beam radiotherapy (EBRT) for EACC. The present study retrospectively reviewed 34 consecutive patients treated for EACC with EBRT between February 2001 and January 2019 at the University of Tokyo Hospital. Clinical staging was performed according to the modified Pittsburgh classification. Of all the included patients, seven patients were in the early stages (I or II) and 27 in the advanced stages (III or IV) of EACC. A total of 16 patients underwent EBRT and surgery (S+RT) pre- and/or postoperatively, while 18 patients underwent definitive radiotherapy (dRT). The median prescribed doses for the S+RT and dRT groups were 66 and 70 Gy, respectively. The median follow-up period for all patients was 22.4 months (range, 2-205 months). The 5-year overall survival rates of the S+RT and dRT groups were 66.7 and 45.1%, respectively. The progression-free survival rate at 5-year was 55.6% (95% confidence interval: 36.5-71.1%) for the entire cohort. A total of 14 patients experienced disease relapse after treatment, consisting of 11 locoregional recurrences and three distant metastases. The current study revealed the clinical outcomes of EBRT for EACC.
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http://dx.doi.org/10.3892/mco.2021.2207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818098PMC
March 2021

Helical skin radiation therapy including total skin radiation therapy using tomotherapy for primary cutaneous lymphoma with bone marrow suppression as a related adverse event.

Pract Radiat Oncol 2021 Jan 10. Epub 2021 Jan 10.

Department of Radiology, University of Tokyo Hospital, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Purpose: Total skin electron beam therapy (TSEBT) is useful for primary cutaneous lymphoma. However, helical skin radiation therapy (HSRT) using tomotherapy may avoid the complexity and uncertainty of TSEBT.

Methods: All patients with primary cutaneous lymphoma who underwent HSRT at our hospital between June 2015 and July 2019 were investigated, including seven patients registered in a clinical trial approved by an institutional review board (ID XXXXXXXXX). HSRT was performed in three partitioned skin areas: head and neck, trunk and arms, and legs.

Results: A total of 24 patients with 53 skin areas (including eight patients with 24 skin areas who had undergone sequential total skin irradiation), with a median follow-up time of 13 months (range 2-50), were investigated. Twenty patients (83.3%) had mycosis fungoides (MF). For 41/53 (77.4%) cases, a dose of 20 Gy/10 fractions was used. The overall response rate in the treated fields of each HSRT in MF patients was 100%, including 38 (80.9%) complete responses (CR), four (8.5%) good partial responses (PR) and five (10.6%) PR. Eight patients with MF who underwent sequential total skin irradiation showed a 100% CR. For MF patients, the median survival time after a first round of HSRT was 22 months (95% CI: 13.6-30.4 months), the median response duration of each HSRT was 5 months (95% CI: 3.67-6.32 months), and the median time to in-field re-irradiation for each HSRT was 15 months (95% CI: 9.76-20.24 months). Bone marrow suppression (>grade 3) often occurred (94.1%) with HSRT on trunk and arms skin. An early patient died due to HSRT causing grade 5 leukopenia.

Conclusions: HSRT, targeting trunk and arms skin, induced severe bone marrow suppression that led to a temporary palliative effect. TSEBT should still be considered standard treatment for primary cutaneous lymphoma covering the total body surface area.
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http://dx.doi.org/10.1016/j.prro.2020.11.007DOI Listing
January 2021

[Improvement in Image Quality of CBCT during Treatment by Cycle Generative Adversarial Network].

Nihon Hoshasen Gijutsu Gakkai Zasshi 2020 ;76(11):1173-1184

Department of Radiology, University of Tokyo Hospital.

Purpose: Volumetric modulated arc therapy (VMAT) can acquire projection images during rotational irradiation, and cone-beam computed tomography (CBCT) images during VMAT delivery can be reconstructed. The poor quality of CBCT images prevents accurate recognition of organ position during the treatment. The purpose of this study was to improve the image quality of CBCT during the treatment by cycle generative adversarial network (CycleGAN).

Method: Twenty patients with clinically localized prostate cancer were treated with VMAT, and projection images for intra-treatment CBCT (iCBCT) were acquired. Synthesis of PCT (SynPCT) with improved image quality by CycleGAN requires only unpaired and unaligned iCBCT and planning CT (PCT) images for training. We performed visual and quantitative evaluation to compare iCBCT, SynPCT and PCT deformable image registration (DIR) to confirm the clinical usefulness.

Result: We demonstrated suitable CycleGAN networks and hyperparameters for SynPCT. The image quality of SynPCT improved visually and quantitatively while preserving anatomical structures of the original iCBCT. The undesirable deformation of PCT was reduced when SynPCT was used as its reference instead of iCBCT.

Conclusion: We have performed image synthesis with preservation of organ position by CycleGAN for iCBCT and confirmed the clinical usefulness.
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http://dx.doi.org/10.6009/jjrt.2020_JSRT_76.11.1173DOI Listing
November 2020

Surface and build-up dose comparison between Elekta 6 MV flattening filter and flattening-filter-free beams using an advanced Markus ionization chamber and a solid water-equivalent phantom.

J Appl Clin Med Phys 2020 Dec 12;21(12):334-339. Epub 2020 Nov 12.

Department of Radiology, University of Tokyo Hospital, Tokyo, Japan.

Using a plane-parallel advanced Markus ionization chamber and a stack of water-equivalent solid phantom blocks, percentage surface and build-up doses of Elekta 6 MV flattening filter (FF) and flattening-filter-free (FFF) beams were measured as a function of the phantom depth for field sizes ranging from 2 × 2 to 10 × 10 cm . It was found that the dose difference between the FF and the FFF beams was relatively small. The maximum dose difference between the FF and the FFF beams was 4.4% at a depth of 1 mm for a field size of 2 × 2 cm . The dose difference was gradually decreased while the field size was increased up to 10 × 10 cm . The measured data were also compared to published Varian FF and FFF data, suggesting that the percentage surface and build-up doses as well as the percentage dose difference between FF and FFF beams by our Elekta linac were smaller than those by the Varian linac.
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http://dx.doi.org/10.1002/acm2.13094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769389PMC
December 2020

Development and evaluation of a prototype detector for an intraoperative laparoscopic coincidence imaging system with PET tracers.

Int J Comput Assist Radiol Surg 2021 Jan 7;16(1):29-39. Epub 2020 Nov 7.

Department of Bioengineering, The University of Tokyo, Bunkyo, Tokyo, Japan.

Purpose: Conventional positron emission tomography can be used only preoperatively to identify lymph node metastases, and hence, these growths are difficult to locate intraoperatively. Previously, an intraoperative laparoscopic coincidence imaging system, with an external fixed detector array and a detector probe that can be moved and inserted into the stomach, was proposed to identify lymph node metastases during stomach cancer surgery. This paper proposes a prototype detector for this system.

Methods: GAGG:Ce (GdAlGaO:Ce) scintillator crystals, one to one coupled with silicon photomultipliers (SiPMs), were used to identify 511 keV photons. An optical tracking system followed the position and orientation of the movable detector. SiPM outputs were read out by time-over-threshold (TOT)-based application-specific integrated circuits, which converted the electrical charges into digital pulses. To identify the arrival time, channel number, and pulse width, which indicate the energy information of each TOT output, a data acquisition system was developed based on a field-programmable gate array.

Results: The spatial resolution of the reconstructed images in lateral direction was better than 7 mm, but that of depth direction was limited, owing to inadequate projections. The prototype successfully reconstructed 44 kBq F-fluorodeoxyglucose sources during a 2-min scan.

Conclusion: We developed a prototype detector for an intraoperative laparoscopic coincidence imaging system. The prototype detector was evaluated successfully, and the produced images were similar to those obtained in the simulation results, thereby suggesting that this method offers a new possibility of imaging lymph node metastases intraoperatively.
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http://dx.doi.org/10.1007/s11548-020-02282-0DOI Listing
January 2021

Sequentially timed all-optical mapping photography boosted by a branched 4f system with a slicing mirror.

Opt Express 2020 Oct;28(21):31914-31922

We present sequentially timed all-optical mapping photography (STAMP) with a slicing mirror in a branched 4f system for an increased number of frames without sacrificing pixel resolution. The branched 4f system spectrally separates the laser light path into multiple paths by the slicing mirror placed in the Fourier plane. Fabricated by an ultra-precision end milling process, the slicing mirror has 18 mirror facets of differing mirror angles. We used the boosted STAMP to observe dynamics of laser ablation with two image sensors which captured 18 subsequent frames at a frame rate of 126 billion frames per second, demonstrating this technique's potential for imaging unexplored ultrafast non-repetitive phenomena.
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http://dx.doi.org/10.1364/OE.400679DOI Listing
October 2020

Shape Estimation Algorithm for Ultrasound Imaging by Flexible Array Transducer.

IEEE Trans Ultrason Ferroelectr Freq Control 2020 11 22;67(11):2345-2353. Epub 2020 Jun 22.

A flexible ultrasonic array transducer able to be attached to the body has the potential to achieve long-term continuous unconstrained ultrasound (US) imaging. However, the quality of reconstructed US images is affected by the accuracy of the estimated array shape because the array shape is primitive for time-delay calculation in delay-and-sum beamforming. In this study, we propose an algorithm for estimating the array shape only from the backscattered US signal without using any external device. The proposed algorithm is based on the assumption that beam-summed images reconstructed using an array shape estimated at higher accuracy would have smaller entropy. The array shape is estimated by searching for the shape with minimal entropy, which was used as the index of the beam-summed image quality. Simulation experiments and phantom experiments were used to evaluate the proposed algorithm. In the simulation experiments, three different array shapes with 2.0 MHz, 20 elements, and 0.8-mm pitch transducers were estimated. In the phantom experiments, the array shapes of commercially available linear, convex, and concave transducers were estimated. The results showed that the proposed algorithm can estimate the correct array shape with an average element position error of less than one-eighth of the wavelength of the transmitted signals. These results indicate that the proposed algorithm can achieve sufficiently accurate shape estimation and has the potential to enable clear US imaging with flexible array transducers.
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http://dx.doi.org/10.1109/TUFFC.2020.3004052DOI Listing
November 2020

Linear accelerator-based stereotactic body radiation therapy in the treatment of oligometastatic disease.

Mol Clin Oncol 2020 Aug 9;13(2):109-114. Epub 2020 Jun 9.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8656, Japan.

The present study reports the clinical outcomes of hypofractionated stereotactic body radiation therapy (SBRT) for oligometastasis (OM) originating from various tumors. Between February 2012 and April 2017, 40 patients with unresectable OM were treated with SBRT. Of these patients, 92% showed a solitary nodal metastasis and the rest had up to three metastases. The dose prescription was 50 Gy in 10 fractions with three-dimensional conformal techniques or volumetric intensity-modulated arc therapy. Median follow-up was 14 months. Of the 40 patients, none showed local progression at the site of SBRT, but 20 patients showed tumor growth at distant sites during follow-up. The 2- and 3-year overall survival rates were 45.1 and 36.1%, respectively. The 2- and 3-year progression-free survival rates were 35.4 and 26.5%, respectively. The interval between diagnosis and detection of OM (<2 vs. >2 years) and primary tumor site (esophagus vs. others) emerged as significant variables affecting survival. Grade 3 subacute and grade 4 chronic toxicities were observed in 1 and 2 patients, respectively. SBRT of 50 Gy in 10 fractions for OM from various primary tumors was shown to lead to good clinical outcomes from the viewpoints of local control and toxicity frequency. However, additional studies are required to identify the patient groups likely to receive maximal benefits from such treatment.
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http://dx.doi.org/10.3892/mco.2020.2065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366231PMC
August 2020

Retrospective dose reconstruction of prostate stereotactic body radiotherapy using cone-beam CT and a log file during VMAT delivery with flattening-filter-free mode.

Radiol Phys Technol 2020 Sep 12;13(3):238-248. Epub 2020 Jul 12.

Department of Radiology, University of Tokyo Hospital, 3-7-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

This study aimed to reconstruct the dose distribution of single fraction of stereotactic body radiotherapy for patients with prostate cancer using cone-beam computed tomography (CBCT) and a log file during volumetric-modulated arc therapy (VMAT) delivery with flattening-filter-free (FFF) mode. Twenty patients with clinically localized prostate cancer were treated with FFF-VMAT, and projection images for in-treatment CBCT (iCBCT) imaging were concomitantly acquired with a log file. A D dose of 36.25 Gy in five fractions was prescribed to each planning target volume (PTV) on each treatment planning CT (pCT). Deformed pCT (dCT) was obtained from the iCBCT using a hybrid deformable image registration algorithm. Dose distributions on the dCT were calculated using Pinnacle v9.10 by converting the log file data to Pinnacle data format using an in-house software. Dose warping was performed by referring to deformation vector fields calculated from pCT and dCT. Reconstructed dose distribution was compared with that of the original plan. Dose differences between the original and reconstructed dose distributions were within 3% at the isocenter and observed in PTV and organ-at-risk (OAR) regions. Differences in OAR regions were relatively larger than those in the PTV, presumably because OARs were more deformed than the PTV. Therefore, our method can be used successfully to reconstruct the dose distributions of one fraction using iCBCT and a log file during FFF-VMAT delivery.
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http://dx.doi.org/10.1007/s12194-020-00574-3DOI Listing
September 2020

An in vitro model of temporal enhancement of epithelium barrier permeability by low-energy shock waves without contrast agents.

Med Biol Eng Comput 2020 Sep 26;58(9):1987-1993. Epub 2020 Jun 26.

Department of Precision Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, 113-8656, Japan.

One of the commonly used techniques for drug delivery is to temporarily increase the permeability of tissue barriers. Acoustic energies such as ultrasound and shock waves are known to modulate tissue permeability. Recently, it was found that shock waves modulate the blood-brain barrier in the rat brain without injection of contrast agents such as microbubbles. This finding implies that modulation of other tissue barriers by shock wave exposure without contrast agents may be possible. To examine whether the modulation is also possible with other tissue barriers, we here investigated whether shock waves would modulate an in vitro tissue barrier model consisting of epithelial cells cultured on culture inserts. The permeability of the epithelium sheets evaluated by trans-epithelial electrical resistance (TEER) was increased following shock waves at a peak pressure of 11 MPa. The increased permeability recovered within 2 h. This enhancement was realized with one-shot low-energy shock waves having an acoustic energy of 0.013 mJ/mm. Monitoring the peak pressures in every exposure revealed that the minimum peak pressure required for the enhancement is 2.9 MPa. These results indicate that shock wave exposure has the potential to temporarily increase the permeability of epithelium barriers to enhance drug delivery without contrast agents. Graphical abstract Enhancements of epithelial barrier permeability were evaluated by trans-epithelial electrical resistance (TEER) before and after shock wave exposures.
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http://dx.doi.org/10.1007/s11517-020-02207-8DOI Listing
September 2020

A novel reaction force-fluorescence measurement system for evaluating pancreatic juice leakage from an excised swine pancreas during distal pancreatectomy.

J Hepatobiliary Pancreat Sci 2020 Nov 10;27(11):877-886. Epub 2020 Jul 10.

Teikyo Heisei University, Toshima-ku, Japan.

Background: Resection using a stapler is a popular approach to distal pancreatectomy. However, the resulting leakage of pancreatic juice represents a serious problem. We have developed a force-fluorescence measurement as a first step towards the quantitative evaluation of pancreatic leakage due to tissue tearing under compression.

Methods: The system comprises a testing machine with an indenter, similar in size to a stapler, which controls compression speed and measures reaction force, and a fluorescence measurement system to measure pancreatic juice leakage. Pancreatic juice leakage is measured as the maximum value of the increasing rate of fluorescence intensity (max value). Ten excised swine pancreases were compressed at a speed of 500, 100, and 10 mm/min until their thicknesses became 2 mm.

Results: A strong positive correlation (0.804) was observed between the increase in max value before and after compression and the amount of reaction force drop due to tissue destruction. No pancreatic juice leakage was observed when compressed slowly (10 mm/min).

Conclusions: We have successfully developed a novel force-fluorescence measurement system that can detect and quantify pancreatic juice leakage caused by tissue tearing. This system can determine the optimal compression conditions for preventing pancreatic juice leakage.
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http://dx.doi.org/10.1002/jhbp.775DOI Listing
November 2020

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study.

Breast 2020 Aug 14;52:88-94. Epub 2020 May 14.

Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. Electronic address:

Background: Because primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC.

Material And Methods: We conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated.

Results: Between January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence.

Conclusion: Breast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence.
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http://dx.doi.org/10.1016/j.breast.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375603PMC
August 2020

Fast Statistical Iterative Reconstruction for Mega-voltage Computed Tomography.

J Med Invest 2020 ;67(1.2):30-39

Department of Radiology, The University of Tokyo Hospital, Japan.

Statistical iterative reconstruction is expected to improve the image quality of computed tomography (CT). However, one of the challenges of iterative reconstruction is its large computational cost. The purpose of this review is to summarize a fast iterative reconstruction algorithm by optimizing reconstruction parameters. Megavolt projection data was acquired from a TomoTherapy system and reconstructed using in-house statistical iterative reconstruction algorithm. Total variation was used as the regularization term and the weight of the regularization term was determined by evaluating signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and visual assessment of spatial resolution using Gammex and Cheese phantoms. Gradient decent with an adaptive convergence parameter, ordered subset expectation maximization (OSEM), and CPU/GPU parallelization were applied in order to accelerate the present reconstruction algorithm. The SNR and CNR of the iterative reconstruction were several times better than that of filtered back projection (FBP). The GPU parallelization code combined with the OSEM algorithm reconstructed an image several hundred times faster than a CPU calculation. With 500 iterations, which provided good convergence, our method produced a 512 × 512 pixel image within a few seconds. The image quality of the present algorithm was much better than that of FBP for patient data. J. Med. Invest. 67 : 30-39, February, 2020.
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http://dx.doi.org/10.2152/jmi.67.30DOI Listing
January 2020

Salvage stereotactic body radiotherapy for post-operative oligo-recurrence of non-small cell lung cancer: A single-institution analysis of 59 patients.

Oncol Lett 2020 Apr 17;19(4):2695-2704. Epub 2020 Feb 17.

Department of Radiology, University of Tokyo Hospital, Tokyo 113-8655, Japan.

A standard treatment for patients with early-stage non-small cell lung cancer (NSCLC) who undergo surgery, and subsequently develop local failure or intrathoracic oligo-recurrence, has not yet been established. The present study aimed to assess the feasibility of stereotactic body radiotherapy (SBRT) for this subgroup of patients. Consequently, a retrospective analysis was conducted of patients with NSCLC recurrence who were treated with SBRT, and previously underwent curative surgical resection between October 2011 and October 2016. Post-SBRT survival [overall survival (OS); progression-free survival (PFS); and local control (LC)] and toxicity were analyzed. Prognostic factors for OS were identified using univariate and multivariate analysis. A total of 52 patients and 59 tumors were analyzed. The median follow-up time was 25 months (35 months for surviving patients), and median OS following salvage SBRT was 32 months. The 1- and 3-year OS rates were 84.4 and 67.8%, respectively. 1- and 3-year PFS rates were 80.8 and 58.7%, respectively. Only 4 patients (7.7%) developed local failure. Median LC was 71 months and 1- and 3-year LC rate were 97.9 and 94.9%, respectively. A total of 4 patients experienced grade 3 or higher adverse events (AEs) and two experienced grade 5 AEs (pneumonitis and hemoptysis). Central tumor location and the possibility of re-operation were independent prognostic factors for OS. The present study indicated that post-operative salvage SBRT is a promising therapeutic option for patients with NSCLC with locoregional or intrathoracic oligo-recurrence. We regard toxicity was also acceptable. However, further research is required on the appropriate selection of subjects, and stratification of the analysis by certain risk factors would increase the accuracy of the conclusions.
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http://dx.doi.org/10.3892/ol.2020.11407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068670PMC
April 2020

Publisher Correction: Prediction of malignant glioma grades using contrast-enhanced T1-weighted and T2-weighted magnetic resonance images based on a radiomic analysis.

Sci Rep 2020 Feb 17;10(1):3073. Epub 2020 Feb 17.

Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-60086-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026034PMC
February 2020

Automatic 3D landmarking model using patch-based deep neural networks for CT image of oral and maxillofacial surgery.

Int J Med Robot 2020 Jun 20;16(3):e2093. Epub 2020 Mar 20.

Department of Oral-Maxillofacial Surgery and Orthodontics, The University of Tokyo Hospital, Tokyo, Japan.

Background: Manual landmarking is a time consuming and highly professional work. Although some algorithm-based landmarking methods have been proposed, they lack flexibility and may be susceptible to data diversity.

Methods: The CT images from 66 patients who underwent oral and maxillofacial surgery (OMS) were landmarked manually in MIMICS. Then the CT slices were exported as images for recreating the 3D volume. The coordinate data of landmarks were further processed in Matlab using a principal component analysis (PCA) method. A patch-based deep neural network model with a three-layer convolutional neural network (CNN) was trained to obtain landmarks from CT images.

Results: The evaluating experiment showed that this CNN model could automatically finish landmarking in an average processing time of 37.871 seconds with an average accuracy of 5.785 mm.

Conclusion: This study shows a promising potential to relieve the workload of the surgeon and reduces the dependence on human experience for OMS landmarking.
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http://dx.doi.org/10.1002/rcs.2093DOI Listing
June 2020

Efficacy of a hydrogel spacer in three-dimensional conformal radiation therapy for prostate cancer.

Jpn J Clin Oncol 2020 Mar;50(3):303-309

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

Objectives: We aimed to compare the dose constraints fulfillment rate of the three-dimensional conformal radiotherapy treatment plan before and after a hydrogel spacer insertion.

Methods: The planning computed tomography scans of 39 patients who received stereotactic body radiotherapy for prostate cancer were used. All patients inserted a hydrogel spacer and underwent computed tomography scans before and after spacer insertion. The three-dimensional conformal radiotherapy plans according to NCCN classification, low-, intermediate- and high-risk, were made for each patient. Clinical target volume included prostate and seminal vesicle 2 cm for high risk, prostate and seminal vesicle 1 cm for intermediate risk and prostate only for low risk. Three-dimensional conformal radiotherapy including a seven-field conformal technique with 76 Gy in 38 fractions. Dose constraints for rectum and bladder were V70 Gy ≤ 15%, V65 Gy ≤ 30% and V40 Gy ≤ 60%.

Results: Among 39 patients, 35 (90%), 19 (49%) and 13 (33%) and 38 (97%), 38 (97%) and 34 (87%) patients before and after the spacer insertion fulfilled rectum dose constraints for low-, intermediate- and high-risk plans, respectively. A hydrogel spacer significantly reduced rectum dose and improved the rectum dose constraints fulfillment rate in intermediate (P < 0.01) and high (P < 0.01), but no difference was found in low-risk plan (P = 0.25). On multivariate analysis, spacer use was associated with the higher rectum dose constraints fulfillment rate.

Conclusions: A hydrogel spacer reduced rectum dose and improved the dose constraints fulfillment rate in three-dimensional conformal radiotherapy plan. Although IMRT is the standard treatment, 3D-CRT using a hydrogel spacer may be a treatment option.
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http://dx.doi.org/10.1093/jjco/hyz171DOI Listing
March 2020

Prediction of malignant glioma grades using contrast-enhanced T1-weighted and T2-weighted magnetic resonance images based on a radiomic analysis.

Sci Rep 2019 12 19;9(1):19411. Epub 2019 Dec 19.

Department of Radiology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

We conducted a feasibility study to predict malignant glioma grades via radiomic analysis using contrast-enhanced T1-weighted magnetic resonance images (CE-T1WIs) and T2-weighted magnetic resonance images (T2WIs). We proposed a framework and applied it to CE-T1WIs and T2WIs (with tumor region data) acquired preoperatively from 157 patients with malignant glioma (grade III: 55, grade IV: 102) as the primary dataset and 67 patients with malignant glioma (grade III: 22, grade IV: 45) as the validation dataset. Radiomic features such as size/shape, intensity, histogram, and texture features were extracted from the tumor regions on the CE-T1WIs and T2WIs. The Wilcoxon-Mann-Whitney (WMW) test and least absolute shrinkage and selection operator logistic regression (LASSO-LR) were employed to select the radiomic features. Various machine learning (ML) algorithms were used to construct prediction models for the malignant glioma grades using the selected radiomic features. Leave-one-out cross-validation (LOOCV) was implemented to evaluate the performance of the prediction models in the primary dataset. The selected radiomic features for all folds in the LOOCV of the primary dataset were used to perform an independent validation. As evaluation indices, accuracies, sensitivities, specificities, and values for the area under receiver operating characteristic curve (or simply the area under the curve (AUC)) for all prediction models were calculated. The mean AUC value for all prediction models constructed by the ML algorithms in the LOOCV of the primary dataset was 0.902 ± 0.024 (95% CI (confidence interval), 0.873-0.932). In the independent validation, the mean AUC value for all prediction models was 0.747 ± 0.034 (95% CI, 0.705-0.790). The results of this study suggest that the malignant glioma grades could be sufficiently and easily predicted by preparing the CE-T1WIs, T2WIs, and tumor delineations for each patient. Our proposed framework may be an effective tool for preoperatively grading malignant gliomas.
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http://dx.doi.org/10.1038/s41598-019-55922-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923390PMC
December 2019

Visual enhancement of Cone-beam CT by use of CycleGAN.

Med Phys 2020 Mar 3;47(3):998-1010. Epub 2020 Jan 3.

Department of Radiology, University of Tokyo Hospital, Tokyo, 113-8655, Japan.

Purpose: Cone-beam computed tomography (CBCT) offers advantages over conventional fan-beam CT in that it requires a shorter time and less exposure to obtain images. However, CBCT images suffer from low soft-tissue contrast, noise, and artifacts compared to conventional fan-beam CT images. Therefore, it is essential to improve the image quality of CBCT.

Methods: In this paper, we propose a synthetic approach to translate CBCT images with deep neural networks. Our method requires only unpaired and unaligned CBCT images and planning fan-beam CT (PlanCT) images for training. The CBCT images and PlanCT images may be obtained from other patients as long as they are acquired with the same scanner settings. Once trained, three-dimensionally reconstructed CBCT images can be directly translated into high-quality PlanCT-like images.

Results: We demonstrate the effectiveness of our method with images obtained from 20 prostate patients, and provide a statistical and visual comparison. The image quality of the translated images shows substantial improvement in voxel values, spatial uniformity, and artifact suppression compared to those of the original CBCT. The anatomical structures of the original CBCT images were also well preserved in the translated images.

Conclusions: Our method produces visually PlanCT-like images from CBCT images while preserving anatomical structures.
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http://dx.doi.org/10.1002/mp.13963DOI Listing
March 2020

Acceptable fetal dose using flattening filter-free volumetric arc therapy (FFF VMAT) in postoperative chemoradiotherapy of tongue cancer during pregnancy.

Clin Transl Radiat Oncol 2020 Jan 14;20:9-12. Epub 2019 Oct 14.

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

Optimizing irradiation protocols for pregnant women is challenging, because there are few cases and a dearth of fetal dosimetry data. We cared for a 36-year-old pregnant woman with tongue cancer. Prior to treatment, we compared three intensity-modulated radiation therapy (IMRT) techniques, including helical tomotherapy, volumetric arc therapy (VMAT), and flattening-filter free VMAT (FFF-VMAT) using treatment planning software. FFF-VMAT achieved the minimum fetal exposure and was selected as the optimal modality. We prescribed 66 Gy to the involved nodes, 60 Gy to the tumor bed and ipsilateral neck, and 54 Gy to the contralateral neck over 33 fractions. To confirm the out-of-field exposure per fraction, surface doses and the rectal dose were measured during FFF-VMAT delivery. Postoperative chemoradiotherapy was delivered using IMRT and a cisplatin regimen. Without any shielding, the total fetal dose was 0.03 Gy, within the limits established by the ICRP. A healthy girl was born vaginally at 37 weeks' gestation.
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http://dx.doi.org/10.1016/j.ctro.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833340PMC
January 2020

Prevention of calpain-dependent degradation of STK38 by MEKK2-mediated phosphorylation.

Sci Rep 2019 11 5;9(1):16010. Epub 2019 Nov 5.

Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Serine-threonine kinase 38 (STK38) is a member of the protein kinase A (PKA)/PKG/PKC-family implicated in the regulation of cell division and morphogenesis. However, the molecular mechanisms underlying STK38 stability remain largely unknown. Here, we show that treatment of cells with either heat or the calcium ionophore A23187 induced STK38 degradation. The calpain inhibitor calpeptin suppressed hyperthermia-induced degradation or the appearance of A23187-induced cleaved form of STK38. An in vitro cleavage assay was then used to demonstrate that calpain I directly cleaves STK38 at the proximal N-terminal region. Deletion of the N-terminal region of STK38 increased its stability against hyperthermia. We further demonstrated that the MAPKK kinase (MAP3K) MEKK2 prevented both heat- and calpain-induced cleavage of STK38. MEKK2 knockdown enhanced hyperthermia-induced degradation of STK38. We performed an in vitro MEKK2 assay and identified the key regulatory site in STK38 phosphorylated by MEKK2. Experiments with a phosphorylation-defective mutant demonstrated that phosphorylation of Ser 91 is important for STK38 stability, as the enzyme is susceptible to degradation by the calpain pathway unless this residue is phosphorylated. In summary, we demonstrated that STK38 is a calpain substrate and revealed a novel role of MEKK2 in the process of STK38 degradation by calpain.
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http://dx.doi.org/10.1038/s41598-019-52435-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831656PMC
November 2019

Optimization of treatment strategy by using a machine learning model to predict survival time of patients with malignant glioma after radiotherapy.

J Radiat Res 2019 Nov;60(6):818-824

Department of Radiology, The University of Tokyo Hospital, Tokyo, Japan.

The purpose of this study was to predict the survival time of patients with malignant glioma after radiotherapy with high accuracy by considering additional clinical factors and optimize the prescription dose and treatment duration for individual patient by using a machine learning model. A total of 35 patients with malignant glioma were included in this study. The candidate features included 12 clinical features and 192 dose-volume histogram (DVH) features. The appropriate input features and parameters of the support vector machine (SVM) were selected using the genetic algorithm based on Akaike's information criterion, i.e. clinical, DVH, and both clinical and DVH features. The prediction accuracy of the SVM models was evaluated through a leave-one-out cross-validation test with residual error, which was defined as the absolute difference between the actual and predicted survival times after radiotherapy. Moreover, the influences of various values of prescription dose and treatment duration on the predicted survival time were evaluated. The prediction accuracy was significantly improved with the combined use of clinical and DVH features compared with the separate use of both features (P < 0.01, Wilcoxon signed rank test). Mean ± standard deviation of the leave-one-out cross-validation using the combined clinical and DVH features, only clinical features and only DVH features were 104.7 ± 96.5, 144.2 ± 126.1 and 204.5 ± 186.0 days, respectively. The prediction accuracy could be improved with the combination of clinical and DVH features, and our results show the potential to optimize the treatment strategy for individual patients based on a machine learning model.
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http://dx.doi.org/10.1093/jrr/rrz066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357235PMC
November 2019

Improvement of the robustness to set up error by a virtual bolus in total scalp irradiation with Helical TomoTherapy.

Radiol Phys Technol 2019 Dec 23;12(4):433-437. Epub 2019 Oct 23.

Department of Radiology, University of Tokyo Hospital, 7-3-1Bunkyo-ku, HongoTokyo, 113-8655, Japan.

Intensity-modulated radiation therapy has recently been used for total scalp irradiation. In inverse planning, the treatment planning system increases the fluence of tangential beam near the skin surface to counter the build-up region. Consequently, the dose to the skin surface increases even with small setup errors. Replacing the electron density of the surrounding air of some thickness with a virtual bolus during optimization could suppress the extremely high fluence near the skin. We confirmed the usefulness of a virtual bolus in total scalp irradiation. For each patient, two beams were planned, one with and the other without a virtual bolus. The dose distribution was calculated using computed tomography images that were shifted to simulate setup errors. The hot spot dose was suppressed in the plans using a virtual bolus. In conclusion, using a virtual bolus improved the robustness to setup errors.
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http://dx.doi.org/10.1007/s12194-019-00539-1DOI Listing
December 2019

Radiomics Analysis for Glioma Malignancy Evaluation Using Diffusion Kurtosis and Tensor Imaging.

Int J Radiat Oncol Biol Phys 2019 11 22;105(4):784-791. Epub 2019 Jul 22.

Department of Neurosurgery, University of Tokyo, Tokyo.

Purpose: A noninvasive diagnostic method to predict the degree of malignancy accurately would be of great help in glioma management. This study aimed to create a highly accurate machine learning model to perform glioma grading.

Methods And Materials: Preoperative magnetic resonance imaging acquired for cases of glioma operated on at our institution from October 2014 through January 2018 were obtained retrospectively. Six types of magnetic resonance imaging sequences (T-weighted image, diffusion-weighted image, apparent diffusion coefficient [ADC], fractional anisotropy, and mean kurtosis [MK]) were chosen for analysis; 476 features were extracted semiautomatically for each sequence (2856 features in total). Recursive feature elimination was used to select significant features for a machine learning model that distinguishes glioblastoma from lower-grade glioma (grades 2 and 3).

Results: Fifty-five data sets from 54 cases were obtained (14 grade 2 gliomas, 12 grade 3 gliomas, and 29 glioblastomas), of which 44 and 11 data sets were used for machine learning and independent testing, respectively. We detected 504 features with significant differences (false discovery rate <0.05) between glioblastoma and lower-grade glioma. The most accurate machine learning model was created using 6 features extracted from the ADC and MK images. In the logistic regression, the area under the curve was 0.90 ± 0.05, and the accuracy of the test data set was 0.91 (10 out of 11); using a support vector machine, they were 0.93 ± 0.03 and 0.91 (10 out of 11), respectively (kernel, radial basis function; c = 1.0).

Conclusions: Our machine learning model accurately predicted glioma tumor grade. The ADC and MK sequences produced particularly useful features.
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http://dx.doi.org/10.1016/j.ijrobp.2019.07.011DOI Listing
November 2019

Development of pancreatic cancer during observation for hepatocellular carcinoma: A retrospective cohort study.

Saudi J Gastroenterol 2019 Nov-Dec;25(6):390-396

Department of Radiology, Graduate School of Medicine, The University of Tokyo, Japan.

Background/aims: We aimed to investigate incidence, characteristics, and possible risk factors of pancreatic cancer in patients under observation for hepatocellular carcinoma (HCC) because the association of hepatitis virus B infection and pancreatic cancer has been reported.

Patients And Methods: We performed a retrospective cohort study in the Gastroenterology Department of a University Hospital in Japan between 2004 and 2012. A total of 1848 patients who underwent treatment for HCC were included at the initiation of treatment for HCC (mean follow-up period, 33.6 months). The patients received trimonthly radiological follow-ups. Newly developed cases of pancreatic cancer during follow-up for HCC were compared with that of an age- and sex-matched theoretical cohort from national statistics. Possible predisposing factors for pancreatic cancer related to HCC were assessed. Cumulative probabilities of developing a pancreatic cancer were compared using log-rank test.

Results: About 13 of 1848 patients developed pancreatic cancer (mean follow-up period, 45.2 months). The risk ratio for all patients was 3.02 (log-rank test: P =0.01). Statistical analyses showed no effects of the following factors on the development of pancreatic cancer: age, sex, follow-up period, alcohol intake, laboratory data, presence of hepatitis virus, characteristics of HCC, type of treatment, number of radiological examinations, and cumulative effective dose.

Conclusions: Increased incidence of pancreatic cancer was found in patients under observation for HCC in a relatively small cohort. HCC or other common underlying conditions might be a risk factor for development of pancreatic cancer.
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http://dx.doi.org/10.4103/sjg.SJG_56_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941454PMC
July 2020

Nonlinear photoacoustic waves for light guiding to deep tissue sites.

Opt Lett 2019 Jun;44(12):3006-3009

Light scattering by tissues limits performance in biological sensing or stimulation. Here we present a photoacoustic technique that increases light transmittance by one order of magnitude and enables light localization in deep tissue. Laser-induced nonlinear acoustic waves are utilized to produce a high refractive index contrast in scattering medium without high-intensity pressure. The size of guiding area is around 60 μm, which is equivalent or smaller than the diameter of multimode fibers. To show potential use in biomedical fields, we performed light guiding and imaging of fluorescence, through swine tissues with thickness more than 1 mm.
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http://dx.doi.org/10.1364/OL.44.003006DOI Listing
June 2019

Robot-assisted radical prostatectomy versus volumetric modulated arc therapy: Comparison of front-line therapies for localized prostate cancer.

Radiother Oncol 2019 11 5;140:62-67. Epub 2019 Jun 5.

Department of Urology, Kyorin University Faculty of Medicine, Tokyo, Japan. Electronic address:

Background: Although radical prostatectomy and external beam radiotherapy are recognized as comparable treatment options for localized prostate cancer, robot-assisted radical prostatectomy (RARP) and volumetric modulated arc therapy (VMAT) as the leading respective techniques have yet to be compared.

Methods: We retrospectively analyzed 860 patients with cT1-4N0M0 prostate cancer who underwent RARP (n = 500) or VMAT (n = 360) between 2011 and 2016. Biochemical recurrence-free survival (bRFS; two consecutive prostate-specific antigen measurements ≥0.2 ng/ml for RARP and Phoenix definition for VMAT) and radiological recurrence-free survival (rRFS; radiologically diagnosed distant metastasis or local recurrence) were compared between the two modalities. Cox proportional hazards model was used for multivariate analysis.

Results: The median follow-up durations were 30 and 47.5 months, and median ages were 67 and 71 years (both P < 0.0001) in the RARP and VMAT groups, respectively. VMAT patients had significantly better bRFS than RARP patients, though their definitions of biochemical recurrence differed. If a unified definition of biochemical recurrence (two consecutive prostate-specific antigen measurements ≥0.2 ng/ml) was applied, RARP patients had significantly better bRFS than VMAT patients. Regarding rRFS, RARP patients had significantly better outcomes than VMAT patients, however, multivariate analysis together with D'Amico's risk classification, age-adjusted Charlson's comorbidity index, and concomitant androgen-deprivation therapy, demonstrated no significant difference between RARP and VMAT.

Conclusions: The rRFS outcomes of RARP and VMAT after a medium-term follow-up period were similar, despite their different patient backgrounds. Further studies with a longer follow-up period are needed to compare these techniques in terms of cancer-specific and overall survivals.
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http://dx.doi.org/10.1016/j.radonc.2019.05.015DOI Listing
November 2019

Ascitic IL-10 Concentration Predicts Prognosis of Patients Undergoing Cell-Free and Concentrated Ascites Reinfusion Therapy.

Ther Apher Dial 2020 Feb 6;24(1):90-95. Epub 2019 Aug 6.

Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Tokyo, Japan.

Cell-free and concentrated ascites reinfusion therapy (CART) is now attracting rising attention as one of the strategies against cancer-related malignant ascites in Japan. Several studies report the safety, effectiveness, and complications of CART applied to patients with malignancies. However, its mechanism reflecting these effects still remains unclear. We evaluated concentration of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, IL-12, tumor necrosis factor (TNF)-α, and immunosuppressive cytokine IL-10 in ascites before CART procedures. We investigated their impacts on survival. IL-1β, IL-6, IL-8, TNF-α, and IL-10 were detected in ascites of the patients undergoing CART. Significant body temperature elevation, one potential complication of CART, was observed among the patients although it was not clinically important. There were no significant correlations between changes in body temperature and the concentration of IL-6, IL-8, and IL-10. The presence of IL-10 in ascites significantly related to longer survival after the first session of CART procedures. However, we observed no other clinically important correlation between cytokine concentrations and changes in WBC and CRP. Concentration of inflammatory cytokines in ascites did not relate to body temperature change, the chief complication of CART. Surprisingly, the presence of IL-10 in ascites related to longer survival after CART. Immunological environment of cancer-related ascites may reflect the outcome of CART and improve survival in those with malignancy.
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http://dx.doi.org/10.1111/1744-9987.12863DOI Listing
February 2020

Ultra-high-speed videography of resin-dentin interface failure dynamics under tensile load.

Dent Mater 2019 07 9;35(7):e153-e161. Epub 2019 May 9.

Department of Cariology and Operative Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

Objectives: Ultra-high-speed (UHS) videography was used to visualize the fracture phenomena at the resin-dentin interface during micro-tensile bond strength (μTBS) test. We also investigated whether UHS videography is applicable for failure-mode analysis.

Methods: Ten human mid-coronal dentin surfaces were bonded using Clearfil SE Bond either in self-etching (SE) or etch-and-rinse (ER) mode. After 24-h water storage, the samples were cut into beams for μTBS test and tested at a cross-head speed of 1 mm/min. The fracture phenomena at the bonded interface were captured using a complementary metal-oxide-semiconductor digital UHS camera at 299,166 frames per second. The failure modes were classified using UHS videography, followed by scanning electron microscopy (SEM) analysis. The failure-mode distributions determined by UHS videography and SEM analysis were statistically analyzed using Fisher's exact test with Bonferroni correction.

Results: The crack-propagation speed exceeded 1,500 km/h. No significant difference was found between the SEM and UHS videography failure-mode distributions in the SE mode. A significant difference appeared between them in the ER mode. Significant differences in the incidence of cohesive failures within the adhesive and at the adhesive-composite interface between the SE and ER modes were identified by both SEM and UHS videography.

Significance: UHS videography enabled visualization of the fracture dynamics at the resin- dentin interfaces under tensile load. However, the resolution at such high frame rate was insufficient to classify the failure mode as precisely as that of SEM. Nevertheless, UHS videography can provide more detailed information about the fracture origin and propagation.
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http://dx.doi.org/10.1016/j.dental.2019.04.006DOI Listing
July 2019

Standardization of imaging features for radiomics analysis.

J Med Invest 2019 ;66(1.2):35-37

Department of Radiology, The University of TokyoHospital, Tokyo, Japan.

Radiomics has the potential to provide tumor characteristics with noninvasive and repeatable way. The purpose of this paper is to evaluate the standardization effect of imaging features for radiomics analysis. For this purpose, we prepared two CT databases ; one includes 40 non-small cell lung cancer (NSCLC) patients for whom tumor biopsies was performed before stereotactic body radiation therapy in The University of Tokyo Hospital, and the other includes 29 early-stage NSCLC datasets from the Cancer Imaging Archive. The former was used as the training data, whereas the later was used as the test data in the evaluation of the prediction model. In total, 476 imaging features were extracted from each data. Then, both training and test data were standardized as the min-max normalization, the z-score normalization, and the whitening from the principle component analysis. All of standardization strategies improved the accuracy for the histology prediction. The area under the receiver observed characteristics curve was 0.725, 0.789, and 0.785 in above standardizations, respectively. Radiomics analysis has shown that robust features have a high prognostic power in predicting early-stage NSCLC histology subtypes. The performance was able to be improved by standardizing the data in the feature space. J. Med. Invest. 66 : 35-37, February, 2019.
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http://dx.doi.org/10.2152/jmi.66.35DOI Listing
December 2019