Altered Functional Connectivity of Hippocampal Subfields in Poststroke Dementia.

BACKGROUND: The hippocampus (HP) plays a critical role in memory and orientational functions and is functionally heterogeneous along the longitudinal anterior-posterior axis. Although the previous study has reported volumetric atrophy in hippocampal subfields of patients with poststroke dementia (PSD), how the functional connectivity (FC) is altered in these subfields remains unclear. PURPOSE: To examine the FC changes of the HP subfields in patients with PSD. STUDY TYPE: Prospective. POPULATION: Seventeen normal controls, 20 PSD, and 24 nondemented poststroke (PSND) patients. FIELD STRENGTH/SEQUENCE: A 3.0 T/ T1-weighted imaging, resting-state functional and diffusion tensor imaging. ASSESSMENT: We first segmented the HP using independent component analysis, and then used granger causality analysis to calculate the directed FCs (dFCs) between the subfields and the whole brain, and compared the dFCs among PSD, PSND, and controls. STATISTICAL TESTS: Student's t-test, chi-square test, one-way ANCOVA, multiple regression, support vector machine, multiple comparison correction, and reproducibility analysis. A P value < 0.05 was considered statistically significant. RESULTS: Our results showed HP was functionally divided into HPhead , HPbody , and HPtail bilaterally along the longitudinal axis. PSD patients showed significant dementia-specific decreases in the inward information flow and increases in the outward information flow associated with the bilateral entire HP/HPhead and left HPbody (P < 0.05). Moreover, we observed significant correlations (P < 0.05) between the cognition score and the dFCs related to the bilateral entire HP and left HPhead in the PSD group. Furthermore, dFCs of the HP and its subfields improved the classification between the PSD and PSND patients (accuracy/sensitivity/specificity: 94%/95%/93%) compared to the clinical and demographic parameters alone. DATA CONCLUSION: These findings suggest that altered transmission and reception of information in the HP. These alternations were specific to individual subfields in PSD patients and may offer insight into the neurophysiological mechanisms underlying PSD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Structural and Functional Deficits in Patients with Poststroke Dementia: A Multimodal MRI Study.

Although many neuroimaging studies have reported structural and functional abnormalities in the brains of patients with cognitive impairments following stroke, little is known about the pattern of such brain reorganization in poststroke dementia (PSD). The present study was aimed at investigating alterations in spontaneous brain activity and gray matter volume (GMV) in PSD patients. We collected T1-weighted and resting-state functional magnetic resonance imaging data from 20 PSD patients, 24 poststroke nondementia (PSND) patients, and 21 well-matched normal controls (NCs). We compared the differences among the groups in GMV and the fractional amplitude of low-frequency fluctuations (fALFF). Then, we evaluated the relationship between these brain measures and cognitive assessments and explored the possible distinguisher for PSD by receiver operating characteristic (ROC) curve analysis. PSD patients showed smaller GMV in the right superior temporal gyrus and lower fALFF values in the right inferior frontal gyrus than both PSND patients and NCs, but such differences were not observed between PSND patients and NCs. Moreover, GMV in the left medial prefrontal cortex showed a significant positive correlation with the Mini-Cog assessment in PSD patients, and GMV in the left CPL displayed the highest area under the ROC curve among all the features for classifying PSD versus PSND patients. Our findings suggest that PSD patients show dementia-specific structural and functional alteration patterns, which may help elucidate the pathophysiological mechanisms underlying PSD.

Assessment of liver fibrosis by variable flip angle T1 mapping at 3.0T.

PURPOSE: To evaluate the possibility of using a variable flip angle (VFA) T1 mapping technique to diagnose liver fibrosis. MATERIALS AND METHODS: Liver fibrosis was induced in rabbits by repetitive administration of carbon tetrachloride (CCl4 ). T1 -weighted magnetic resonance imaging (MRI) was performed in 29 animals (liver fibrosis, n = 18; control, n = 11) using a series of nonenhanced liver acquisition volume acceleration (LAVA) with VFAs at 3.0T. Hepatic T1 relaxation times were measured via regions of interest, which were correlated with subsequent histologic confirmation. The results of T1 mapping in assessment of liver fibrosis were compared with that of apparent diffusion coefficient (ADC) values. RESULTS: The mean T1 relaxation time of the control group was the lowest (250.07 ± 88.12 msec), followed by the nonadvanced fibrosis group (387.83 ± 166.58 msec) and the advanced fibrosis group (496.90 ± 291.24 msec). T1 relaxation time measurements differed significantly between the liver fibrosis group and control group (P < 0.05), with a trend of increased mean T1 relaxation times as the fibrotic stage increased. Statistically significant differences were observed between the control group and the nonadvanced fibrosis group (P < 0.05), however with much overlap between the less severe stages. In discriminating between the control group and liver fibrosis group, stage F0-1 (control and stage F1) and stage F2-3, stage F0-2 (control and stage F1-2) and stage F3, area under the receiver operating characteristic (ROC) curves were 0.803 (cutoff value 273.01 msec), 0.712 (cutoff value 371.54 msec), and 0.696 (cutoff value 276.99 msec), respectively. No difference was found between T1 relaxation times and ADC values in assessment of liver fibrosis in our study. CONCLUSION: VFA T1 mapping may become a noninvasive imaging tool for the diagnosis of liver fibrosis.

Assessment of liver fibrosis using pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: To evaluate the pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in diagnosing and staging liver fibrosis in rabbits. MATERIALS AND METHODS: DCE-MRI with gadodiamide (Gd-DTPA-BMA) was performed on a 3.0 Tesla, 60 cm bore MR scanner for rabbits with CCl4 -induced liver fibrosis, and an untreated control group. Fibrosis was staged according to the METAVIR system: control (F0; n = 13), nonadvanced fibrosis (F1-2; n = 15), and advanced fibrosis (F3-4; n = 12). The DCE-MRI parameters K(trans) , kep , Ve , and vp were measured with a dual-input extended Tofts model. Receiver operating characteristic analyses were performed to assess the diagnostic performance of K(trans) , Ve , and vp in staging liver fibrosis. RESULTS: Both K(trans) and Ve decreased with increasing fibrosis stage. K(trans) of the control group was significantly different from that of the overall fibrosis group, nonadvanced group, and advanced group (P < 0.001 for all). Significant differences were found between Ve of the control group and that of the overall fibrosis and advanced groups (P = 0.019 and P = 0.009, respectively). For K(trans) , the areas under the receiver operating characteristic curve (AUROCs) for discriminating the control group from the overall fibrosis and advanced fibrosis groups were 0.909 (95% confidence interval [CI], 0.809-1.000), and 0.936 (95% CI,0.847-1.000), respectively. For discriminating between the control and nonadvanced fibrosis groups, the AUROC of K(trans) was 0.887 (95% CI, 0.762-1.000). The AUROCs of K(trans) were higher than those of Ve and vp for discriminating between the control and overall fibrosis groups, the control and nonadvanced fibrosis groups, and the control and advanced fibrosis groups. Pharmacokinetic parameters were negatively correlated with fibrosis stage (K(trans) , rho = -0.668, P < 0.001; Ve , rho = -0.438, P = 0.005; vp , rho = -0.360, P = 0.023). CONCLUSION: Among pharmacokinetic parameters of DCE-MRI in our study, K(trans) was an excellent predictor for differentiating fibrotic livers from normal livers, and differentiating normal livers from nonadvanced or advanced fibrosis livers. J. Magn. Reson. Imaging 2016;44:98-104.

Large-diameter compression arteries as a possible facilitating factor for trigeminal neuralgia: analysis of axial and radial diffusivity.

BACKGROUND: Neurovascular compression (NVC) of the trigeminal nerve is associated with trigeminal neuralgia (TN). Some arteries that compress the trigeminal nerve are large, while others are small. This study evaluated the influence of diameter of compression arteries (DCA) on NVC with and without TN using axial diffusivity (AD) and radial diffusivity (RD) of magnetic resonance (MR) imaging. METHODS: Fifty TN patients with unilateral NVC, 50 asymptomatic patients with unilateral NVC, and 50 healthy controls (HC) were divided into three groups (NVC with TN, NVC without TN, and HC). The three groups were imaged with a 3.0-T MR system using three-dimensional fast imaging employing steady-state acquisition (3D FIESTA) and diffusion tensor imaging (DTI). We compared the mean size of DCA between NVC with and without TN. The mean values of AD and RD at the site of NVC were compared between the three groups. Correlation analyses were performed between the DCA and the diffusion metrics (AD and RD) in NVC patients with and without TN. RESULTS: The mean DCA in NVC patients with TN (1.58 ± 0.34 mm) was larger than that without TN (0.89 ± 0.29 mm). Compared with NVC without TN and HC, the mean values of RD at the site of NVC with TN were significantly increased; however, no significant changes of AD were found between the groups. Correlation analysis showed that DCA positively correlated with RD in NVC patients with and without TN (r = 0.830, p = 0.000). No significant correlation was found between DCA and AD (r = 0.178, p = 0.077). CONCLUSIONS: Larger-diameter compression arteries may increase the chances of TN, and may be a possible facilitating factor for TN.

Atrophic Pattern of Hippocampal Subfields in Post-Stroke Demented Patient.

BACKGROUND: Previous studies have demonstrated that hippocampal atrophy is a hallmark of dementia and can be used to predict the outcome of post-stroke demented (PSD) patients. The hippocampus consists of several subfields but their involvement in the pathophysiology of the PSD remains unclear. OBJECTIVE: The present study aimed to investigate volumetric alterations of hippocampal subfields in patients with PSD. METHODS: High-resolution T1-weighted images were collected from 27 PSD and 28 post-stroke nondemented (PSND) patients who recovered from ischemic stroke, and 17 age-matched normal control (NC). We estimated the volumes of the hippocampal subfields using FreeSurfer 6.0 which segmented the hippocampus into 12 subfields in each hemisphere. The volumetric differences between the groups were evaluated by the two-sample tests after regressing out the age, sex, education, and total intracranial volume. RESULTS: Compared with NC group, PSD group showed smaller volumes in the entire hippocampus and its subfields, and such differences were not found in PSND group. Moreover, we found the dementia-specific atrophy in the left granule cell layer of dentate gyrus (GC-DG) and CA4 in the PSD patients compared with NC and PSND. Regression analysis showed positive correlations between the changes of cognitive performance and the asymmetry index in the CA3/4 and GC-DG of the PSD group. Furthermore, we found that the volumes of hippocampal subfields provided a better classification performance than the entire hippocampus. CONCLUSION: Our findings suggest that the hippocampus is reduced in the PSD patients and it presents a selective subfield involvement.

Gait characteristics and clinical relevance of hereditary spinocerebellar ataxia on deep learning.

BACKGROUND: Deep learning has always been at the forefront of scientific research. It has also been applied to medical research. Hereditary spinocerebellar ataxia (SCA) is characterized by gait abnormalities and is usually evaluated semi-quantitatively by scales. However, more detailed gait characteristics of SCA and related objective methods have not yet been established. Therefore, the purpose of this study was to evaluate the gait characteristics of SCA patients, as well as to analyze the correlation between gait parameters, clinical scales, and imaging on deep learning. METHODS: Twenty SCA patients diagnosed by genetic detection were included in the study. Ten patients who were tested via functional magnetic resonance imaging (fMRI) were included in the SCA imaging subgroup. All SCA patients were evaluated with the International Cooperative Ataxia Rating Scale (ICARS) and Scale for the Assessment and Rating of Ataxia (SARA) clinical scales. The gait control group included 16 healthy subjects, and the imaging control group included seven healthy subjects. Gait data consisting of 10 m of free walking of each individual in the SCA group and the gait control group were detected by wearable gait-detection equipment. Stride length, stride time, velocity, supporting-phase percentage, and swinging-phase percentage were extracted as gait parameters. Cerebellar volume and the midsagittal cerebellar proportion in the posterior fossa (MRVD) were calculated according to MR. RESULTS: There were significant differences in stride length, velocity, supporting-phase percentage, and swinging-phase percentage between the SCA group and the gait control group. The stride length and stride velocity of SCA groups were lower while supporting phase was longer than those of the gait control group. SCA group's velocity was negatively correlated with both the ICARS and SARA scores. The cerebellar volume and MRVD of the SCA imaging subgroup were significantly smaller than those of the imaging control group. MRVD was significantly correlated with ICARS and SARA scores, as well as stride velocity variability. CONCLUSION: SCA gait parameters were characterized by a reduced stride length, slower walking velocity, and longer supporting phase. Additionally, a smaller cerebellar volume correlated with an increased irregularity in gait. Gait characteristics exhibited considerable clinical relevance to hereditary SCA. We conclude that a combination of gait parameters, ataxia scales, and MRVD may represent more objective markers for clinical evaluations of SCA.

[In vivo study of innervation of degenerative intervertebral discs in rabbit anular-injury model].

OBJECTIVE: To observe degenerative intervertebral disc and to examine innervation of degenerative discs in the rabbit anular-injury model. METHODS: Two different magnitudes of anular injury at 5 mm depth were performed by 11 blade or 16 gauge needle at the L3-L4 or L5-L6 discs in New Zealand white rabbits (n=48, 2.5-3.0 kg). Disc degeneration was evaluated by radiographic, MRI and histological examination at different time points after surgery. To identify nerve ingrowth into disc, two general markers PGP 9.5 and GAP 43, for nerve fibers were examined by immunohistochemistry. RESULT: Significant decreases in disc height and signal intensity in magnetic resonance imaging were observed in 11 blade group and 16 G puncture group (P<0.01). 16 G puncture group induced slower and more progressive disc degeneration companed with the stab group and control group. At the 12-week time point, nucleus pulposus tissues were extruded and scar tissues formed outside the disc. In stab discs, nerve ingrowth was scattered on the surface of injury site and in the deeper part of the scar tissues, more than 1 mm from the surface. However, in punctured discs, PGP 9.5 and GAP 43-immunoreative fibers were only observed in the outmost part of the scar tissues and superficial area. More nerve fibers were observed in stab group. CONCLUSION: Innervation may act as a source of discogenic pain which is associated with intervertebral disc degeneration caused by disc anular injury.

Diffusion-weighted imaging and variable flip angle T1 mapping: a supplement for image-guided biopsy in follow-up analysis of liver fibrosis.

Purpose To evaluate the performance of diffusion-weighted imaging (DWI) and variable flip angle (VFA) T1 mapping as a supplement to image-guided biopsy in follow-up analysis of liver fibrosis. Materials and Methods This prospective study was approved by the institution's committee on human research, and written informed consent was provided from the enrolled patients. We investigated five MRI parameters of DWI and VFA T1 mapping, collected from 11 patients who underwent serial ultrasound image-guided biopsy with follow-up MRI within 1.5 years after treatment for liver fibrosis/cirrhosis. For each patient, four consecutive MRI examinations were conducted, including baseline MRI before treatment and three follow-up MRI examinations after treatment at each 0.5-year interval. ADC values at four b values and T1 relaxation times were correlated to pathology-confirmed liver fibrosis stages, which were subsequently divided into two groups, stages F2-3 and F4. The receiver operating characteristic (ROC) analysis and repeated measurement analysis of variance were used for statistical analysis. Results Among these ADC parameters, ADC value (b = 500 s/mm2) was the most consistent in differentiating between stage F2-3 and F4 liver fibrosis. Repeated measurement analysis showed that the intra-group and inter-group differences were 0.447 and 0.024, respectively. T1 relaxation time could not consistently differentiate between the F2-3 and F4 groups; however, it was repeatable, and the intra-group and inter-group differences were 0.410 and 0.042, respectively. Conclusion MRI-ADC value at a b value of 500 s/mm2 can be a promising biomarker for differentiating stages F2-3 and F4 liver fibrosis. A combination of this biomarker with repeatable T1 relaxation time may function as a non-invasive tool for follow-up liver fibrosis in patients who reject repeated image-guided biopsy.

Fe3+@polyDOPA-b-polysarcosine, a T1-Weighted MRI Contrast Agent via Controlled NTA Polymerization.

α-Amino acid N-thiocarboxyanhydrides (NTAs) are promising cyclic monomers to synthesize polypeptides and polypeptoids via controlled ring-opening polymerizations. Superior to N-carboxyanhydrides requiring protection on hydroxyl groups, NTAs are able to tolerate such nucleophiles. In this work, we report the synthesis of NTA monomers containing unprotected phenolic hydroxyl groups of 3,4-dihydroxy-l-phenylalanine (DOPA) and l-tyrosine (Tyr). Their controlled ROPs and sequential copolymerizations with polysarcosine (PSar) yield PDOPA, PTyr, and PDOPA-b-polysarcosine (PDOPA-b-PSar) products quantitatively with designable degrees of polymerization. Micellar nanoparticles of Fe3+@PDOPA-b-PSar have been prepared thanks to the strong chelation of iron(III) cation by catechol ligands that act as T1-weighted magnetic resonance imaging (MRI) contrast agents. For instance, Fe3+@PDOPA10-b-PSar50 exhibits higher longitudinal relaxivity (r1 = 5.6 mM-1 s-1) than commercial Gd3+-based compounds. Effective MRI contrast enhancement in vivo of nude mice with a moderate duration (150 min) and 3D magnetic resonance angiography in rabbit illustrated by using volume rendering and maximal intensity projection techniques ignite the clinical application of Fe3+-based polypept(o)ides in diagnostic radiology as Gd-free MRI contrast agents.

Radiofrequency heat-enhanced direct intratumoral chemotherapy for prostate cancer.

A novel, minimally invasive interventional technique, radiofrequency heat (RFH), has been suggested to improve the efficacy of chemotherapy for solid organ tumors. However, the treatment for prostate cancer has not been completely characterized. The aim of the present study was to investigate the in vitro and in vivo efficiency of chemotherapy in combination with RFH for the treatment of prostate cancer. The following four treatment groups were included: i) No treatment (control); ii) RFH-only; iii) chemotherapy (docetaxel)-only; and iv) combination therapy of docetaxel and RFH in human prostate cancer (HPC) cell lines and mice with HPC xenografts. In the in vitro experiments, a heating guidewire was attached under the bottom of the last chamber of the four-chamber cell culture slide, and was then connected to a radiofrequency (RF) generator. In the in vivo experiments, a tumor model was generated by subcutaneously injecting human prostate cancer cells into 24 male nu/nu mice. RFH was conducted by inserting the 0.022-inch heating-guidewire into the tumor. The follow-up magnetic resonance imaging demonstrated a significant reduction in the average tumor size in animals treated with combination therapy compared with those receiving RFH-only and chemotherapy-only. The number of apoptotic cells and the average apoptotic index of the combination therapy group were significantly higher compared with those of the other three treatment groups. In conclusion, the results of the present study suggested that RFH is able to increase the therapeutic efficiency of docetaxel in prostate cancer, and this study serves as a foundation for the future development of an interventional molecular image-guided local treatment strategy for prostate cancer that integrates RF technology, interventional oncology and direct intratumoral chemotherapy, as a replacement for systemic chemotherapy.

Dimethylfumarate induces cell cycle arrest and apoptosis via regulating intracellular redox systems in HeLa cells.

Dimethylfumarate (DMF) is cytotoxic to several kinds of cells and serves as an anti-tumor drug. This study was designed to investigate the effects and underlying mechanism of DMF on cervical cancer cells. HeLa cells were cultured and treated with 0, 50, 100, 150, and 200 µM DMF, respectively. After 24 h, cell growth was evaluated using Cell Counting Kit-8 (CCK-8) assay and the cell cycle was examined using flow cytometry. In addition, cell apoptosis was detected by Annexin V/propidium iodide (PI) staining and the expressions of caspase-3 and poly-ADP-ribose polymerase (PARP) were detected using western blotting. The redox-related factors were then assessed. Furthermore, all of the indicators were detected in HeLa cells after combined treatment of DMF and N-acetyl-L-cysteine (NAC, an oxygen-free radical scavenger). The cell number and cell growth of HeLa were obviously inhibited by DMF in a dose-dependent manner, as the cell cycle was arrested at G0/G1 phase (P < 0.05). The apoptotic HeLa cells were markedly increased, and the expression levels of caspase-3 and PARP were significantly increased in a DMF concentration-dependent way (P < 0.05). Meanwhile, loss of △Ψm, increase in reactive oxygen species and O2·-, and the decrease in catalase activity and glutathione (GSH) level were found after DMF treatment (P < 0.05). All these changes were significantly attenuated and even completely disappeared by adding NAC (P < 0.05). In conclusion, the cytotoxicity of DMF on cell proliferation and apoptosis of HeLa cells was mainly related to the intracellular redox systems by depletion of intracellular GSH.

Radiofrequency hyperthermia promotes the therapeutic effects on chemotherapeutic-resistant breast cancer when combined with heat shock protein promoter-controlled HSV-TK gene therapy: Toward imaging-guided interventional gene therapy.

OBJECTIVE: Gene therapy is a frontier in modern medicine. In the present study, we explored a new technique for the effective treatment of multidrug-resistant (MDR) breast cancer by combining fully the advantages of multidisciplinary fields, including image-guided minimally invasive interventional oncology, radiofrequency technology, and direct intratumoral gene therapy. RESULTS: Combination treatment with PHSP-TK plus RFH resulted in significantly higher TK gene transfection/expression, as well as a lower cell proliferation rate and a higher cell apoptosis index, than those of control groups. In vivo validation experiments with MRI confirmed that combination therapy resulted in a significant reduction of relative tumor volume compared with those of control animals, which was supported by the results of histologic and apoptosis analyses. MATERIALS AND METHODS: The heat shock protein promoter (PHSP) was used to precisely control the overexpression of thymidine kinase (TK) (PHSP-TK). Serial in vitro experiments were performed to confirm whether radiofrequency hyperthermia (RFH) could enhance PHSP-TK transfection and expression in a MDR breast cancer cell line (MCF7/Adr). Serial in vivo experiments were then carried out to validate the feasibility of the new technique, termed interventional RFH-enhanced direct intratumoral PHSP-TK gene therapy. The therapeutic effect of combination therapy was evaluated by MRI and confirmed by subsequent laboratory correlation. CONCLUSIONS: This study has established "proof-of-principle" of a new technique, interventional RFH-enhanced local gene therapy for MDR breast cancer, which may open new avenues for the effective management of MDR breast cancers via the simultaneous integration of interventional oncology, RF technology, and direct intratumoral gene therapy.

Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

Research into europium complexes as magnetic resonance imaging contrast agents (Review).

Europium (Eu) is a paramagnetic lanthanide element that possesses an outstanding luminescent property. Eu complexes are ideal fluorescence imaging (FI) agents. Eu2+ has satisfactory relaxivity and optical properties, and can realize magnetic resonance (MRI)-FI dual imaging applications when used with appropriate cryptands that render it oxidatively stable. By contrast, based on the chemical exchange saturation transfer (CEST) mechanism, Eu3+ complexes can provide enhanced MRI sensitivity when used with optimal cryptands, incorporated into polymeric CEST agents or blended with Gd3+. Eu complexes are promising in MRI-FI dual imaging applications and have a bright future.

Radiofrequency heat-enhanced chemotherapy for breast cancer: towards interventional molecular image-guided chemotherapy.

Breast cancer is the most common malignancy in women worldwide. Recent developments in minimally invasive interventional radiology techniques have significantly improved breast cancer treatment. This study aimed to develop a novel technique for the local management of breast cancers using radiofrequency heat (RFH). We performed both in vitro experiments using human breast cancer cells and in vivo validation in xenograft animal models with magnetic resonance imaging (MRI) and pathological correlation to investigate the feasibility of our approach. Four treatment groups, including (1) no treatment (control), (2) RFH-only, (3) chemo (doxorubicin)-only, and (4) combination therapy with both doxorubicin and RFH, were conducted in each experiment. In vitro combination therapy significantly decreased breast cancer cell proliferation while increased their apoptosis index compared to the other three groups. MRI demonstrated a significant tumor size reduction in animals treated with combination therapy compared to those receiving other treatments in vivo. Such result was further confirmed by pathological examination. In conclusion, our findings suggests that RFH can enhance the therapeutic efficiency of doxorubicin on breast cancers, thus establishing the basis for future development of interventional molecular image-guided local chemotherapy for breast malignancies.