A multicenter randomized phase II trial of hyperthermia combined with TPF induction chemotherapy compared with TPF induction chemotherapy in locally advanced resectable oral squamous cell carcinoma.

BACKGROUND: Hyperthermia has been reported to cause cancer stage regression, thus providing surgical opportunities in patients with unresectable tumors and improving the quality of life of patients by preserving certain organs. METHODS: A prospective open-label phase II trial was conducted to evaluate the efficacy of hyperthermia combined with induction chemotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients received hyperthermia combined with two cycles of 5-fluorouracil, cisplatin, and docetaxel (TPF) induction chemotherapy regimens or TPF induction chemotherapy alone, followed by radical surgery with postoperative radiotherapy. The primary endpoint was the clinical response rate of the induction chemotherapy. The secondary endpoints were overall survival (OS), disease-free survival (DFS), and toxicity. RESULTS: A total of 120 patients were enrolled, and 115 patients were included in the clinical response analysis. The clinical response rate was significantly higher in the experimental arm than in the control arm (65.45% vs. 40.00%, p = 0.0088). There were no unexpected toxicities, and hyperthermia and induction chemotherapy did not increase the perioperative morbidity rate. Moreover, there was a significant improvement in DFS, but no significant difference in OS between the two arms. In the subgroup analysis, increased OS and DFS rates were associated with patients with favorable clinical response after induction chemotherapy in the total population, experimental arm, and control arm. CONCLUSIONS: Our study demonstrates that hyperthermia combined with induction chemotherapy is associated with a high response rate and provides a new treatment option for patients with resectable stage III or IVA OSCC.

Multiple instance learning for computer aided detection and diagnosis of gastric cancer with dual-energy CT imaging.

Multiple instance learning algorithms have been increasingly utilized in computer aided detection and diagnosis field. In this study, we propose a novel multiple instance learning method for the identification of tumor invasion depth of gastric cancer with dual-energy CT imaging. In the proposed scheme, two level features, bag-level features and instance-level features are extracted for subsequent processing and classification work. For instance-level features, there is some ambiguity in assigning labels to selected patches. An improved Citation-KNN method is presented to solve this problem. Compared with benchmarking state-of-the-art multiple instance learning algorithms using the same clinical dataset, the proposed algorithm can achieve improved results. The experimental evaluation is performed using leave-one-out cross validation with the total accuracy of 0.7692. The proposed multiple instance learning algorithm serves as an alternative method for computer aided diagnosis and identification of tumor invasion depth of gastric cancer with dual-energy CT imaging techniques.

The efficacy and hyperthermic release of doxorubicin from liposomal doxorubicin hydrochloride in rabbit VX2 tumours.

PURPOSE: To establish optimum conditions for anti-tumour therapy, we evaluated the efficacy of doxorubicin using liposomal doxorubicin and local hyperthermia to improve the anti-tumour efficacy over liposomal doxorubicin alone in rabbit VX2 tumours. MATERIALS AND METHODS: A VX2 tumour model was established in New Zealand white rabbits, which were randomly divided into five groups: 1) control, 2) free doxorubicin hydrochloride (Dox), 3) liposomal doxorubicin hydrochloride (L-Dox), 4) L-Dox plus 41 °C thermotherapy (L-Dox + 41 °C TT); and 5) L-Dox plus 43 °C thermotherapy (L-Dox + 43 °C TT). To achieve complete tumour remission, multiple high-dose administrations (5 mg/kg, once per week for a total of 3 weeks) were given. An ultrasound hyperthermia instrument was used to induce local hyperthermia and the systemic toxicity of Dox was evaluated by changes in weight, blood count and serum lactic dehydrogenase. The anti-tumour effect of Dox was evaluated by observing the gross tumour volume, weight and rabbit survival. RESULTS: The white blood cell count following administration of Dox or L-Dox was lower than for control animals and those treated with L-Dox + 41 °C TT. There was no difference between the groups with regard to the red blood cell count. Compared with the control and Dox groups, tumour proliferation was significantly inhibited following administration of L-Dox, L-Dox + 41 °C TT and L-Dox + 43 °C TT, as evidenced by the difference in tumour volume, weight and survival time. Differences in tumour proliferation were also found between the L-Dox and thermotherapy groups. CONCLUSION: Local hyperthermia combined with L-Dox can significantly improve anti-tumour efficacy and reduce systemic toxicity.

Identification of the molecular subtypes and signatures to predict the prognosis, biological functions, and therapeutic response based on the anoikis-related genes in colorectal cancer.

BACKGROUND: Tumors that resist anoikis, a programmed cell death triggered by detachment from the extracellular matrix, promote metastasis; however, the role of anoikis-related genes (ARGs) in colorectal cancer (CRC) stratification, prognosis, and biological functions remains unclear. METHODS: We obtained transcriptomic profiles of CRC and 27 ARGs from The Cancer Genome Atlas, the Gene Expression Omnibus, and MSigDB databases, respectively. CRC tissue samples were classified into two clusters based on the expression pattern of ARGs, and their functional differences were explored. Hub genes were screened using weighted gene co-expression network analysis, univariate analysis, and least absolute selection and shrinkage operator analysis, and validated in cell lines, tissues, or the Human Protein Atlas database. We constructed an ARG-risk model and nomogram to predict prognosis in patients with CRC, which was validated using an external cohort. Multifaceted landscapes, including stemness, tumor microenvironment (TME), immune landscape, and drug sensitivity, between high- and low-risk groups were examined. RESULTS: Patients with CRC were divided into C1 and C2 clusters. Cluster C1 exhibited higher TME scores, whereas cluster C2 had favorable outcomes and a higher stemness index. Eight upregulated hub ARGs (TIMP1, P3H1, SPP1, HAMP, IFI30, ADAM8, ITGAX, and APOC1) were utilized to construct the risk model. The qRT-PCR, Western blotting, and immunohistochemistry results were consistent with those of the bioinformatics analysis. Patients with high risk exhibited worse overall survival (p < 0.01), increased stemness, TME, immune checkpoint expression, immune infiltration, tumor mutation burden, and drug susceptibility compared with the patients with low risk. CONCLUSION: Our results offer a novel CRC stratification based on ARGs and a risk-scoring system that could predict the prognosis, stemness, TME, immunophenotypes, and drug susceptibility of patients with CRC, thereby improving their prognosis. This stratification may facilitate personalized therapies.

Transcostal high-intensity focused ultrasound treatment using phased array with geometric correction.

In the high-intensity focused ultrasound treatment of liver tumors, ultrasound propagation is affected by the rib cage. Because of the diffraction and absorption of the bone, the sound distribution at the focal plane is altered, and more importantly, overheating on the rib surface might occur. To overcome these problems, a geometric correction method is applied to turn off the elements blocked by the ribs. The potential of steering the focus of the phased-array along the propagation direction to improve the transcostal treatment was investigated by simulations and experiments using different rib models and transducers. The ultrasound propagation through the ribs was computed by a hybrid method including the Rayleigh-Sommerfeld integral, k-space method, and angular spectrum method. A modified correction method was proposed to adjust the output of elements based on their relative area in the projected "shadow" of the ribs. The simulation results showed that an increase in the specific absorption rate gain up to 300% was obtained by varying the focal length although the optimal value varied in each situation. Therefore, acoustic simulation is required for each clinical case to determine a satisfactory treatment plan.

[Framework design of MRI guided phased HIFU system and software development].

This paper introduced a new structure of MRI guided P-HIFU therapy system and software implementation based on the current P-HIFU system and interface provided by MRI vendor. The tests showed that the system's software can achieve the appropriate form of treatment need.

[A positioning method of ultrasound probe in MR system].

This paper provides a method of positioning the ultrasound probe in MR system. Machining 6 slots or cylinder perpendicular to the ultrasound probe surface on the edge of ultrasound probe as markers, 12 central cylinder ends are chosen as positioning points. By calculating these positioning points' coordinates in MR's coordinate system, the coordinate transformation between the ultrasound and MR coordinate system can be computed. Furthermore, by taking advantage of redundant information, calculating errors can be reduced and the precision can be improved.

CRISPR/Cas9: a powerful tool in colorectal cancer research.

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide and seriously threatens human health. The clustered regulatory interspaced short palindromic repeat/CRISPR-associate nuclease 9 (CRISPR/Cas9) system is an adaptive immune system of bacteria or archaea. Since its introduction, research into various aspects of treatment approaches for CRC has been accelerated, including investigation of the oncogenes, tumor suppressor genes (TSGs), drug resistance genes, target genes, mouse model construction, and especially in genome-wide library screening. Furthermore, the CRISPR/Cas9 system can be utilized for gene therapy for CRC, specifically involving in the molecular targeted drug delivery or targeted knockout in vivo. In this review, we elucidate the mechanism of the CRISPR/Cas9 system and its comprehensive applications in CRC. Additionally, we discussed the issue of off-target effects associated with CRISPR/Cas9, which serves to restrict its practical application. Future research on CRC should in-depth and systematically utilize the CRISPR/Cas9 system thereby achieving clinical practice.

Effects of different parameters in the fast scanning method for HIFU treatment.

PURPOSE: High-intensity focused ultrasound is a promising method for the noninvasive treatment of benign and malignant tumors. This study analyzes the effects of scanning path, applied power, and geometric characteristics of the transducer on ablation using fast scanning method, a new scanning method that uses high-intensity focused ultrasound at different blood perfusion levels. METHODS: Two transducers, six scanning paths, and three focal patterns were used to examine the ablation results of the fast scanning method using power densities from 1.35 × 10(7) W∕m(3) to 4.5 × 10(7) W∕m(3) and blood perfusion rates from 2 × 10(-3) ml∕ml∕s to 16 × 10(-3) ml∕ml∕s. The Pennes equation was solved using the finite-difference time-domain method to simulate the heating procedure. RESULTS: Based on the results of the fast-scanning method, the different scanning paths exhibited small effect on the total treatment time supported by both simulation and least-square fit. Similar-sized lesions can result from the five different repeated paths, whereas a random path may lead to relative large fluctuations in ablation volume because of asymmetry of the lesions. Higher power levels increase the lesion volume and decrease the treatment time required for ablating a target area using the fast scanning method, whereas increased blood perfusion has the opposite effect on ablation volume and treatment time. A symmetric lesion can be produced through fast scanning method using a 65-element and a 90-element transducer. However, lesion production using the same operation scheme differs between the two transducers. CONCLUSIONS: Unlike traditional scanning methods, fast scanning method produces a planned lesion regardless of scanning path, as long as the path consists of repeated subsequences. This attribute makes fast scanning method an easy-operation scheme that produces relatively large symmetric lesions in homogeneous tissues. Applied power is the most important factor; however, high blood perfusion levels can limit or even hinder the full ablation of the target area. Therefore, tissue perfusion and transducer type should be given special attention to ensure the success and safety of ablation treatment.

[The development of phase signal generator for the phased HIFU system based on FPGA].

The FPGA-based phased-signal generator described in this paper meets the requirement of massive output channels and high resolution of HIFU. After experimental measurements, this phased-signal generator can output 256 channels of phase signals and each channel has a phase resolution of 2nS. The phased-signal generator also has many other advantages such as simple implementation method and high reliability.

Real-time elastography for the differentiation of benign and malignant breast lesions: a meta-analysis.

The prognostic significance of ultrasound real-time elastography (RTE) in patients with breast lesions is controversial. There are two different diagnostic methods: the elasticity score (ES) and the strain ratio (SR). A meta-analysis was performed using a random-effect model to assess the overall sensitivity and specificity of RTE in the differentiation of breast lesions. MEDLINE, EMBASE, PubMed, and the Cochrane Library before February 2011 were searched. A total of 22 studies, which included 4,713 breast nodules in 4,266 patients were analyzed. The overall mean sensitivity and specificity for the diagnosis of malignant breast lesions by RTE were 0.834 [95% confidence interval (CI) 0.814-0.853] and 0.842 (95% CI, 0.829-0.854) for ES, and 0.883 (95% CI, 0.844-0.916) and 0.814 (95% CI, 0.786-0.839) for SR, respectively. RTE has a high sensitivity and specificity in the evaluation of breast lesions and can potentially reduce unnecessary breast biopsies.

Suppressing Grating Lobes for Transcranial Focused Ultrasound System by Frequency-Modulated Excitation.

Transcranial focused ultrasound is a novel noninvasive therapeutic modality for glioblastoma and other disorders of the brain. However, because the phase aberrations caused by the skull need to be corrected with computed tomography (CT) images, the transcranial transducer is tightly fixed on the patient's head to avoid any variation in the relative position, and the focus shifting relies mainly on the capacity for electronic beam steering. Due to the presence of grating lobes and the rapid degradation of the focus quality with increasing focus-shifting distance, transcranial focus-shifting sonication may damage healthy brain tissue unintentionally. To reduce the risks associated with transcranial focused ultrasound therapy, linear frequency-modulated (FM) excitation is proposed. The k-space corrected pseudospectral time domain (PSTD) and acoustic holography approach based on the Rayleigh integral are combined to calculate the distribution of the deposited acoustic power. The corresponding simulation was performed with axial/lateral focus shifting at different distances. The distributions of the deposited acoustic power show that linear FM excitation can effectively suppress undesired prefocal grating lobes without compromising focus quality.

Design of a Versatile Angle-Rotatable Skull-Shaped Conformal Transcranial Focused Ultrasound Transducer for Noninvasive Brain Therapy.

Phase-controlled focused ultrasound transducers have opened up a new way to noninvasively treat brain diseases. However, due to the geometry and the heterogeneous medium of the human skull, the currently used hemispherical transducers cannot guarantee that the ultrasound emitted by the transducer penetrates the skull normally; consequently, the impact of the shear wave on the treatment area has to be considered. The usual approach is to turn off elements in the transducer with excessively large incident angles, but this approach reduces the efficiency of the transducer. This article presents the design of a novel transducer that can be rotated according to the different geometric shapes of the skull. The incident angles of the elements in the transducer are modified so that the effect of the shear wave on the treatment area can be ignored and the efficiency of the transducer is improved. The results of computed tomography (CT) model simulation of nine skulls verify the versatility and feasibility of the new transducer. We believe that this kind of rotatable transducer has clinical and engineering significance.

[Measurement and analysis of phased-array focused ultrasound field of two-foci pattern].

This paper introduces the simulation and measurement results of the phased-array focused ultrasound field of two-foci pattern.

[Development and application of the phased HIFU system software].

This paper introduces HIFU system software based on a phased-array HIFU device. Combined with the database and computer graphics technology, this HIFU system software can be used to develop the therapy planning semi-automatically, implement the pilot project efficiently and accelerate the clinical studies.

An efficient and accurate parallel hybrid acoustic signal correction method for transcranial ultrasound.

Phased-control focused ultrasound transducers provide a new and noninvasive treatment method for brain disease. However, improving the accuracy of phase correction and reducing the calculation time during treatment have always been contradictory constraints. In this paper, a hybrid acoustic signal correction (HASC) method combined with k-Wave stage and holography stage was introduced for phase correction and simulation of transcranial focused ultrasound. The k-Wave stage is mainly used to calculate the sound field in a heterogeneous medium (skull), which divides the sound field calculation process into paths that can be calculated in parallel, and the transcranial correction phase can also be obtained during the calculation. The holography stage is sufficient to simulate the acoustic field in the homogenous intracranial medium after ultrasound transmitting through the skull. The agreement of the k-space corrected pseudospectral time domain method and HASC method was assessed by statistical methods: linear regression between the two methods provided a slope of 0.9735, intercept of 0.0078, and R 2 of 0.9982. The Bland-Altman method provided a bias of 0.0015 and 95% limits of agreement 0.065 apart. We demonstrated that the difference in sound intensity at the focal point corrected by HASC and time reversal phase correction method was 0.2% and 0.5% in the results of simulation and experiment, respectively. Not only that, the phase calculation time by the HASC phase correction method can be reduced to 11 min on a multi GPU array, which has clinical potential for ultrasound treatment of brain therapy.

[Digital image analysis of trabecular microstructure].

Trabecular microstructure is an important factor that influences the bone biomechanical properties. In this paper, studies on digital image analysis of trabecular microstructure are reviewed with special emphases on the serials parameters as well as on the measurement methods of trabecular microstructure characteristic. The future researches and advances are also prospected.

Evaluating Targeting Accuracy in the Focal Plane for an Ultrasound-guided High-intensity Focused Ultrasound Phased-array System.

Phased arrays are increasingly used as high-intensity focused ultrasound (HIFU) transducers in the existing extracorporeal ultrasound-guided HIFU (USgHIFU) systems. The HIFU transducers in such systems are usually spherical in shape with a central hole where a US imaging probe is mounted and can be rotated. The image on the plane of treatment can be reconstructed through the image sequence acquired during the rotation of the probe. Therefore, the treatment plan can be made on the reconstructed images. In order to evaluate the targeting accuracy in the focal plane of such systems, the protocol of a method using a bovine muscle and marker-embedded phantom is described. In the phantom, four solid balls at the corners of a square resin model serve as the reference markers in the reconstructed image. The target should be moved so that both its center and the center of the square model can coincide according to their relative positions in the reconstructed image. Swine muscle with a thickness of about 30 mm is placed above the phantom to mimic the beam path in clinical settings. After sonication, the treatment plane in the phantom is scanned and the boundary of the associated lesion is extracted from the scanned image. The targeting accuracy can be evaluated by measuring the distance between the centers of target and lesion, as well as three derivative parameters. This method cannot only evaluate the targeting accuracy of the target consisting of multiple focal spots rather than a single focal spot in a clinically relevant beam path of the USgHIFU phased-array system, but it can be also used in the preclinical evaluation or regular maintenance of USgHIFU systems configured with phased-array or self-focused HIFU transducer.

The shape of the acetabular cartilage surface: a geometric morphometric study using three-dimensional scanning.

The acetabular cartilage surface plays an important role in hip joint biomechanics, locomotion and lubrication, but few studies has focused on its geometric morphometry. The aim of this study was to present a novel, accurate mathematical representation of the acetabular cartilage surface based on a new method, combined with a reverse engineering technique, surface-fitting algorithms and mathematical curve surface theory. By using a three-dimensional (3D) laser scanner, a 3D triangulated mesh surface approximation of acetabular cartilage was created. Using surface-fitting algorithms and mathematical curve surface theory, two main curvature parameters, Gaussian curvature and mean curvature at each point on the surface of the acetabular cartilage, were calculated. The distribution patterns of both parameters over the curved surface were elucidated and the eigenvalues of the surface were calculated to determine the shape of the acetabular cartilage surface. By statistically analyzing 25 specimens, it was found that the shape of the acetabular cartilage surface was not theoretically spherical but rotational ellipsoidal, which is a novel mathematical description. The surface-fitting error of a rotational ellipsoid shape was significantly smaller than that of a spherical shape for representing the acetabular cartilage surface (p<0.001). The highest surface-fitting error for a spherical shape was seen in the roof area of the acetabular cartilage, where a rotational ellipsoid surface presented a better anatomical fit. The results will not only be helpful in gaining a new anatomical understanding of the acetabular cartilage surface, but will also be usable in the construction of a precise 3D numerical model in simulation studies of the hip joint.

Mutual information-based multimodal image registration using a novel joint histogram estimation.

Mutual information (MI)-based image registration has been proved to be very effective in multimodal medical image applications. For computing the mutual information between two images, the joint histogram needs to be estimated. As we know, the joint histogram estimation through linear interpolation and partial volume (PV) interpolation methods may result in the emergency of the local extreme in mutual information registration function. The local extreme is likely to hamper the optimization process and influence the registration accuracy. In this paper, we present a novel joint histogram estimation method (HPV) by using an approximate function of Hanning windowed sinc as kernel function of partial volume interpolation. We apply it to both rigid registration and non-rigid registration. In addition, we give a new method estimating the gradient of mutual information with respect to the model parameters during non-rigid registration. By the experiments on both synthetic and real images, it is clearly shown that the new algorithm has the ability to reduce the local extreme, and the registration accuracy is improved.