Challenges and countermeasures to the clinical teaching of oncology / 中华医学教育探索杂志

Aiming at the contradiction between the current oncology teaching model and the rapid development of modern oncology, this study proposes to use precision medicine principles, integrated medicine (MDT treatment) and problem-based, evidence-based CSCO guide learning in clinical oncology teaching. Through specific cases, students are instructed to study the guidelines, and cultivate students' concepts of evidence-based medicine, students' interest in participating in oncology teaching, and they can initially form treatment strategies. The prospects have been put forward from the establishment of a clinical oncology curriculum system, the construction of a single-disease diagnosis and treatment teaching environment and a team of teaching staff, the reinforcement of students' basic experiments and evidence-based clinical data cross-application learning, and the enhancement of humanistic quality education.

Study on denervated rat skeletal muscle by 7.0 T 31P-MR phosphorus spectroscopy / 中华放射学杂志

Objective@#To investigate the changes of 31P-MRS in denervated skeletal muscle at 7.0 T MR system.@*Methods@#In the experiment group, a total of 18 male Sprague-Dawley rats aged 6-8 weeks old and weighing 200-250 g were obtained. The right posterior femoral nerve were transected, and the proximal stumps were ligated by using 5-0 nylon stitches to preclude spontaneous repair. A sham surgery (incision and exploration of the nerve) was performed at the same time (n=6). Before rat model established and at varying times after initial surgery (3 d, and 1, 2, 4, 6, and 8 weeks). 31P-MR spectra of rat quadriceps femoris were acquired on 7.0 T Agilent small animal MR imaging system. We quantified the phosphocreatine (PCr), adenosine triphosphate(β-ATP), and inorganic phosphate (Pi) using Creatine phosphate disodium salt(10 mmol/L) as an external standard. The ratios, include PCr/Pi, Pi/β-ATP, PCr/β-ATP, PCr/(PCr+Pi) and Pi/(PCr+Pi) were quantified in jMRUI. All data were analyzed by one way analysis of variance (ANOVA) with posttest inter-group comparisons using Bonferroni test. Comparative analysis methods between the experimental and control group were performed via independent samples t test. P<0.05 was considered as statistically significance.@*Results@#The average measured concentrations of β-ATP, PCr, and Pi in control groups were (6.654±0.178) μmol/g, (25.656±0.738) μmol/g, and (1.594±0.096) μmol/g, respectively. There were significant statistically differences in β-ATP, PCr, Pi, PCr/Pi, PCr/PCr+Pi,Pi/PCr+Pi between the study and control group(P<0.05) at any measurement time point after denervation. Pi/β-ATP,PCr/β-ATP and pHi in the experimental group significantly statistically differed from those of the control group (all P<0.05)at each time point except on day 3 after operation. The total concentrations of β-ATP and PCr were reduced by 11.5% and 19.7% respectively on day 3. Thereafter, β-ATP and PCr declined rapidly by 63.1% and 68.8% at week 4 respectively, then decreased slowely by 74.0%和82.3% till week 10. The change of PCr/Pi is similar to β-ATP and PCr, but more remarkable. Pi, Pi/PCr+Pi, Pi/ATP showed a progressively increase till week 10. The intra-cellular pH (pHi) of normal rat muscles was 7.033±0.017, While the pHi gently in experiment rat muscles decreased during the entire experiment.@*Conclusion@#31P-MRS with 7.0 T can quantify the temporal changes of energy metabolism and pHi in normal and denervated rat muscles. It shows that the dysfunction of energy metabolism are progressive with time and that they begin within a short period following the nerve section, the change of β-ATP, PCr, PCr/Pi take place primarily within 4 weeks after denervation. β-ATP, PCr, and PCr/Pi may be potential biomarkers of energy metabolism in the evaluation of denervated muscle atrophy.

Evaluation of diffusion kurtosis imaging and its combination with diffusion weighted imaging and proton MR spectroscopy in differentiation of breast lesions / 中华放射学杂志

Objective To evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) and its combination with DWI and proton MR spectroscopy (1H-MRS) in differentiating malignancy from benign breast lesions. Methods Fifty-three patients with 38 histopathologically confirmed malignant and 15 benign breast lesions were retrospectively studied. The patients were examined by breast MRI at 3.0 T prior to operation, including conventional T1WI, fat-suppression imaging, DWI, DKI and 1H-MRS. The shape and margin of breast lesions, and their corresponding mean values for ADC, mean kurtosis (MK) and mean diffusivity (MD) were determined by two blinded radiologists in consensus. The presence or absence of choline (Cho) peak was identified using LCModel software. Independent-samples t test or χ2 test was performed for the comparison of clinical characteristics, shape and margin of lesions, and imaging parameters between malignancy and benign lesions. ROC analysis was performed to evaluate the diagnostic accuracy of DKI, DWI and 1H-MRS alone or in combination, in comparison with the histopathologic findings. Results The onset age of breast malignancy was higher than that of benign ones, and the difference has statistical significant (P0.05). The mean ADC,MD and MK of benign lesions were(1.464 ± 0.348)× 10-3mm2/s,(1.726 ± 0.268)× 10-3mm2/s and(0.692 ± 0.227), the mean ADC,MD and MK of malignancy were(0.963 ± 0.170)× 10-3mm2/s,(1.158 ± 0.262)× 10-3mm2/s and(1.311 ± 0.218), respectively. Significant differences were obtained between benign and malignant lesions for all parameters (P<0.05).The area under the ROC curve (AUC) of ADC, MD and MK for differentiating malignancy from benign lesions was 0.913, 0.933 and 0.968, respectively. Taken the maximum Youden's index of MK (1.110) as the ROC optimal cut-off point, MK exhibited better diagnostic sensitivity, specificity and accuracy for distinguishing malignancy from benign lesions [89.5%(34/38),93.3%(14/15) and 90.6%(48/53), respectively], compared with MD and ADC. Multiparametric imaging with combination of DKI, DWI and 1H-MRS improves the diagnostic specificity (with the highest as 100.0%) but decreases the sensitivity (with the highest as 81.6% and lowest as 71.1% ), compare with the single parametric imaging. Conclusions MK generated from DKI enables differentiation of breast lesions with a higher diagnostic sensitivity and specificity than DWI and 1H-MRS. DKI combined with DWI and 1H-MRS increase specificity but decrease sensitivity for breast cancer characterization.

Application of 9.4 T 1 H-MR spectroscopy in determination of lactate in brain of mice with early acute hypoxia-ischeia injury and its significance / 吉林大学学报(医学版)

Objective:To explore the lactate metabolism in brain tissue of the mice with early acute hypoxia-ischemia injury,and to provide data support for 9.4T 1 H-NMR spectroscopy in detecting the lactate level clinically.Methods:Eighty Kunming mice were randomly divided into sixteen groups (0 s,20 s,40 s,60 s,2 min,4 min, 6 min,8 min, 10 min, 12 min, 14 min, 16 min, 18 min,and 20 min)according to the duration of hypoxia-ischemia (n=5).The changes of lactate levels were detected by 9.4T 1 H-NMR spectroscopy. Results:After the initiation of hypoxia-ischemia injury,the lactate level began to increase rapidly to the highest value of (6.89 ± 0.34)μmol·g-1 at 20 s,then started to decline quickly from 40 s to 2 min,and eventually decreased to a stable level of (4.85±0.36)μmol·g-1 until 6 min.Compared with control group,the levels of lactate in brain tissue of the mice in hypoxic-ischemic groups were increased (P <0.01).Conclusion:40 s of acute hypoxia-ischemia may be the lactate cerebral neuron threshold during the anaerobic glycolysis. 9.4T1 H-MRS can provide the exact time window for detecting the lactate metabolism.

Quantitative analysis of brain metabolites in systemic lupus erythematosus patients using multivoxel MR spectroscopy / 中华风湿病学杂志

Objective To investigate the metabolite changes in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric symptoms using magnetic resonance spectroscopy (MRS) and explore the associations between image findings and clinical variables. Methods Twenty-two SLE patients with neuropsychiatric symptoms (NPSLE), twenty-one SLE patients without neuropsychiatric symptoms (non-NPSLE) and twenty healthy controls (HCs) underwent routine MRI scan and multivoxel magnetic reson-ance spectroscopy (MVS). The absolute metabolite concentrations were measured bilaterally in the posterior cingulate gyrus (PCG), dorsal thalamus (DT), lentiform nucleus (LN) and posterior paratrigonal white matter (PWM) using LCModel and SAGE software. The relationships between metabolite con-centrations and cognitive function scores were analyzed by Spearman rank correlation. Single-factor Chi-square analysis and t-test were used for analysis. Results ① Compared to control subjects, NPSLE patients had significantly lower N-acetylaspartate (NAA) values in bilateral PCG and DT, with the mean differences of -1.504 [95% confidence interval ( CI) (-2.335, -0.672), P=0.001], -1.460 [95%CI (-2.349, -0.570), P=0.002], -1.259 [95%CI (-1.894, -0.625), P=0.000] and -1.022[95%CI (-1.688, -0.356), P=0.003] for RPCG, LPCG, RDT and LDT, respectively. The concentration of total creatinine were observed to decline in RPCG and RDT, with the mean differences of-1.094 [95%CI (-1.845, -0.342), P=0.003], -0.955 [95%CI (-1.630, -0.280), P=0.006], -1.259 [95%CI (-1.894,-0.625), P=0.006] respectively. Glutamine and glutamate-values decreased significantly in RDT [mean difference=-2.586, 95%CI (-4.139, -1.033), P=0.002]. ② Compared to non-NPSLE patients, NPSLE patients had a lower NAA level in LPCG [mean difference=-1.256, 95%CI (-2.146, -0.367), P=0.006]. Positive correlations between mini-mental state examination scores [RPCG: rs=0.312, P<0.05; LPCG: rs=0.355, P<0.01], Montreal cognitive assessment scores (RPCG: rs=0.362, P<0.01; LPCG: rs=0.285, P<0.05) and NAA values in bilateral PCG were detected. Conclusion Both NPSLE and non-NPSLE patients may have metabolite dysfun-ctions in different brain regions. The cognitive disorder in SLE patients may be interpreted by neuronic damage of PCG.

Metabolite profiles of mesenchymal stem cells underwent death on 9.4T MR spectroscopy / 中华放射学杂志

Objective To explore the metabolite profiles of mesenchymal stem cells(MSCs)underwent death using 9.4 T high resolution MR spectroscopy.Methods MSCs were cultured and treated for 6,12 and 24 hours in a stimulated condition which included hypoxia,serum deprivation and changes of microenvironment.Cell death and the mortality was detected by light microscopy,Hocchst staining and flow cytometry analyses.The morality of stem cells was analyzed using one-way analysis of variance (ANOVA).Cell metabolite extraction was prepared by methanol-chloroform(M/C) method and analyzed on a 9.4 T MR device.1H-MR spectroscopy was obtained and the metabolite concentration of each time point was calculated and compared using one way ANOVA,the difference between two groups was analyzed by SNK test.Results Necrosis was the major form of cell death in the built model.The morality of every time sets was 16±4(0 h),658±61 (6 h),1 571 ± 154(12 h) and 2 816± 178(24 h) respectively,and the difference between each groups were statistically significant (F=298.96,P＜0.01).After induced stem cells death for 6,12 and 24 h,the metabolite concentrations at 0.89 ppm was (1.48±0.69),(2.32±0.63)and (2.15±0.45)nmol/mg respectively,and increased compared to thc control[(1.41 ±0.25)nmol/mg]with statistical significance (F=329.57,P＜0.01).The metabolite concentrations at 1.28 ppm was (6.42±0.31),(7.26±0.32)and (7.01 ±0.61)nmol/mg,respectively,and increased compared to the control[(5.76 ±0.74)nmol/mg]with statistical significance (F=19.56,P＜0.01).The metabolite concentrations at 1.60 ppm was (2.36±0.31),(2.29±0.16)and (2.31 ± 0.24) nmol/mg respectively,and increased compared to the control[(1.96 ± 0.27)nmol/mg]with statistical significance (F=4.35,P＜0.05).After induced stem cells death for 12 hours,the metabolite concentrations at 0.89 ppm was increased compared to 6 hours with statistical significance (P＜0.05).The metabolite concentrations at 1.28 ppm was increased compared to 6 hours with statistical significance (P＜0.05).After induced stem cells death for 24 hours,the metabolite concentrations at 0.89 ppm was decreased compared to 12 hours with statistical significance (P＜0.05).Conclusions There are some specific characteristics on MRS of MSCs underwent death,and the fatty acid peak may serve as a biomarker for cell death.

Image-Guided Percutaneous Lipiodol-Pingyangmycin Suspension Injection Therapy for Sacral Chordoma

A 74-year-old man presented with a progressively worsening pain in sacrum and was diagnosed to have a sacral chordoma by biopsy in May, 2004. Percutaneous intratumoral injection with lipiodol-pingyangmycin suspension (LPS) was carried out under image guidance and repeated when the pain in sacrum recurred and the tumor increased. During a 6-year follow-up period, three sessions of this treatment were executed. CT imaging and Karnofsky Performance Score were used to evaluate the size of tumor and quality of life, respectively. The patient was free of pain after each procedure and had a high quality of life with a Karnofsky Performance Score above 80 points. The tumor lesion in sacral area was effectively controlled. No complications were observed. Percutaneous intratumoral injection with LPS under image guidance may be an effective and safe alternative for the patients with sacral chordoma.

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with conventional beams for nasopharyngeal carcinoma: a feasibility study / 癌症

There is increasing interest in the clinical use of flattening filter-free (FFF) beams. In this study, we aimed to investigate the dosimetric characteristics of volumetric modulated arc radiotherapy (VMAT) with FFF beams for nasopharyngeal carcinoma (NPC). Ten NPC patients were randomly selected to undergo a RapidArc plan with either FFF beams (RA-FFF) or conventional beams (RA-C). The doses to the planning target volumes (PTVs), organs at risk (OARs), and normal tissues were compared. The technical delivery parameters for RapidArc plans were also assessed to compare the characteristics of FFF and conventional beams. Both techniques delivered adequate doses to PTVs. For PTVs, RA-C delivered lower maximum and mean doses and improved conformity and homogeneity compared with RA-FFF. Both techniques provided similar maximum doses to the optic nerves and lenses. For the brain stem, spinal cord, larynx, parotid glands, oral cavity, and skin, RA-FFF showed significant dose increases compared to RA-C. The dose to normal tissue was lower in RA-FFF. The monitor units (MUs) were (536 ± 46) MU for RA-FFF and (501 ±25) MU for RA-C. The treatment duration did not significantly differ between plans. Although both treatment plans could meet clinical needs, RA-C is dosimetrically superior to RA-FFF for NPC radiotherapy.

Pharmacokinetics and Bio-distribution of New Gd-complexes of DTPA-bis (amide) (L3) in a Rat Model

PURPOSE: To investigate the blood pharmacokinetics and bio-distribution of DTPA-bis-amide (L3) Gd(III) complexes. MATERIALS AND METHODS: The pharmacokinetics and bio-distribution of Gd (L3)(H2O).nH2O were investigated in Sprague-Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. The Gd content in the blood, various tissues, and organs was determined by ICP-AES. Blood pharmacokinetic parameters were calculated using a two-compartment model. RESULTS: The half-lives of alphaphase and betaphase Gd (L3)(H2O).nH2O were 2.286+/-0.11 min and 146.1+/-7.5 min, respectively. The bio-distribution properties reveal that the complex is mainly excreted by the renal pathway, and possibly excreted by the hepatobiliary route. The concentration ratio of Gd (III) was significantly higher in the liver and spleen than in other organs, and small amounts of Gd (III) ion were detected in the blood or other tissues of rats only after 7 days of intravenous administration. CONCLUSION: The MRI contrast agent Gd (L3)(H2O).nH2O provides prolonged blood pool retention in the circulation and then clears rapidly with minimal accumulation of Gd(III) ions. The synthesis of gadolinium complexes with well-balanced lipophilicity and hydrophilicity shows promise for their further development as blood pool MRI contrast agents.

Investigation of the metabolic changes in visual cortex due to visual stimulation using high field magnetic resonance spectroscopy at 7.0 T / 中华放射学杂志

Objective To investigate the metabolic changes in the visual cortex due to visual stimulation using high field functional proton magnetic resonance spectroscopy at 7.0 T.A clear picture of brain metabolism and neurotransmitter activity during activation was expected to be established.Methods Nine healthy subjects participated in this study. All MR measurements were acquired using a 7.0 T MR system and a 16-channel SENSE head coil. An initial fMRI scan was performed prior to spectroscopic acquisition in order to determine the activated region in the visual cortex.A cubic ROI of 2 cm× 2 cm × 2 cm was positioned inside the activated region for functional MRS acquisition.A short TE STEAM sequence was used for acquiring the MRS data. The functional paradigm comprised 6.6 min baseline followed by 13.2 min of visual stimulation and 19.8 min recovery.Summed averaged spectra for visual stimulus off and visual stimulus on were analyzed separately using LC Model and internal reference of water. A Wilcoxon signed rank test was conducted to compare the metabolite changes. ResultsDuring stimulation,concentration in Asp [ ( 3.20 ± 0.28 ) μmol/g ],Gln [ ( 2.07 ± 0.10 ) μmol/g ] and Gly [ ( 1.65 ± 0.11 )μmol/g ] was found to be significantly decreased,compared with that of ( 3.52 ± 0.28 ),( 2.25 ± 0.10 ) and ( 1.85 ± 0.11 ) μmol/g in rest ( Z =- 2.073,- 2.073 and - 2.429,respectively,P ＜ 0.05 ).The level in Glu [ ( 11.50 ± 0.11 ) μmol/g],GSH[ (2.45 ± 0.10) μmol/g] and Lac[ (0.89 ± 0.05) μ.mol/g]due to neuronal activation was found to be significantly increased,versus resting concentration of ( 11.28 ± 0.11 ),( 2.28 ± 0.10 ) and (0.79 ± 0.05 ) μmol/g,respectively ( Z =2.521,2.310,2.016,respectively,P ＜0.05).Glc level [ (1.54 ± 0.23 )μmol/g] exhibited a tendency to decrease throughout the period of stimulation,compared with that of [ (1.78 ± 0.28 ) μmol/g ] in rest,but the decrease did not reach statistical significance (Z =- 1.897,P ＞ 0.05 ).ConclusionsUsing a novel visual stimulation paradigm and 1 H MRS at 7.0 T and LC Model,the metabolic response to activation have been able to be observed.The observed changes of Asp,Glc and Lac concentrations in response to visual stimulation suggests that sustained neuronal activation raises oxidative metabolism to a new steady state.The observation of increased Glu with decreased Gln during stimulation can be interpreted as a stimulus driven increase in excitatory neurotransmitter cycling.The elevated GSH in the visual cortex in response to visual stimulation is a new observation.Possible explanations for this include detoxification of reactive oxygen species.

Review of absolute quantification of brain metabolites by using multi-voxel 1H-MRS / 国际生物医学工程杂志

The technology of Magnetic Resonance Spectroscopy(MRS) is a newly-developed mean for analyzing some specific nucleus and their compounds making use of the principles of magnetic resonance and the effects of chemical shift. Currently, among MRS applications, proton magnetic resonance spectroscopy (1HMRS) is the most widely applied one developed from single voxel to three-dimensional multi-voxel scanning technique. It provides a lot of important information for clinical studies. This article mainly reviews the methods for absolute quantification measurement of brain metabolites using multi-voxel MRS.

Quantitative analysis of brain metabolites concentrations using MR spectroscopy in acute hypoxia ischemic encephalopathy / 中华放射学杂志

Objective To evaluate the absolute quantification of brain metabolites concentrations using external standard MRS in acute hypoxia ischemia encephalopathy (HIE) piglet model. Method Eight 7-day-old healthy piglets were subjected to insult of hypoxia ischemia (HI). The animals and an external standard phantom containing detectable metabolites of known concentrations were studied on a 1.5 T GE Signa scanner. The single-voxel proton magnetic resonance spectroscopy (1H-MRS) data were processed using LCModel software, and the quantification of N-acetylaspartate ( NAA), creatine (Cr) and lactate (Lac) were accomplished. Multivariate analysis of variance was performed to compare the NAA, Cr, Lac concentration differences in the brains of piglets pre- and post-HI (0h). In addition, the dynamic changes of brain metabolites concentrations of 2 HIE piglets were observed at the time points of 0 h and 2 h. Results One piglet was excluded because it was over anesthetized to death. Seven piglets' data were analyzed. The concentrations of NAA pre- and post-HI were ( 6. 86 ± 0. 49 ) mmol/kg and ( 5.73 ± 0. 88 ) mmol/kg respectively, they were ( 4. 65 ± 0. 73 ) mmol/kg and ( 4. 40 ± 0. 80 ) mmol/kg for Cr; and were 0. 00 mmol/kg and (0. 43 ± 0. 39) mmol/kg for Lac. After HI, decreased NAA concentration immediately was observed, and it was of statistical significance ( F = 8. 608, P = 0. 013 ). The concentration of Cr was insignificantly decreased ( F = 0. 379, P = 0. 550). The concentration of Lac was increased, and the difference was of statistical significance ( F = 8. 600 ,P = 0. 013 ). Dynamic observation showed a Lac peak immediately after HI and it decreased after 2 h post-HI. Conclusions External standard MRS using LCModel has great value in the quantitative analysis of brain metabolites. The changes of NAA and Lac concentrations are sensitive to reflect the early metabolic change of acute HIE.

Experimental investigation of the accuracy for absolute quantification of brain creatine concentration using long time echo point resolved spectroscopy sequence with an external standard and linear combination of model spectra / 中华放射学杂志

Objective To investigate the accuracy for absolute quantification of brain creatine (Cr) concentration using long time echo (TE) point resolved spectroscopy (PRESS) sequence performed with an external standard and postprocessed with the linear combination of model spectra (LCModel).Methods Ten swine (3.1±0.6 kg) and an external standard phantom containing detectable compounds of known concentration were investigated in this study by using 1.5 T GE Signa scanner and a standard head coil. The single-voxel proton magnetic resonance spectroscopy (1H-MRS) data were acquired from the two ROIs (2 cm×2 cm×2 cm) placed in swine brain and external standard solution using PRESS sequence with TE 135 ms,TR 1500 ms,and 128 scan averages.The in vivo quantification of Cr was accomplished by LCModel.After 1H-MRS examination,each animal was sacrificed immediately.In vitro Cr concentration was analyzed by high performance liquid chromatography (HPLC).Results In the 1H-MRS group,the Cr concentration was (9.37±0.14)mmol/kg.In the HPLC group,the Cr concentration was (8.91±0.13)mmol/kg.Good agreement was obtained between these two methods (t=9.038,P=0.491).Conclusion The long echo time PRESS sequence performed with an external standard and processed with LCModel iS proven to be an accurate technique to detect the in vivo brain Cr concentration.

Comparison of gradient echo and echo planar imaging measurements for the calculation of regional blood volume maps / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to evaluate relative regional blood volume (rCBV) in meningioma and compare the utility of reconstruction using both gradient-echo sequence and echo-planar-imaging (EPI) sequence. Eighteen patients with meningiomas were studied on a Siemens 1.5-T scanner. During the gradient-echo sequence (n=12) and EPI sequence (n=6), a bolus (0.2 mmol/kg) of Gd-DTPA was injected mechanically with a flow rate of 5 ml/second. Image processing of dynamic data was performed on a pixel-by-pixel basis. The ratio of tumor rCBV/gray matter rCBV was 3.01 +/- 1.18 (3.07 +/- 1.39 in gradient sequence and 2.84 +/- 0.94 in EPI sequence). The ratio of gray matter/white matter as the reference tissue had a mean of 2.79 +/- 0.76 using the FLASH sequence, and a mean of 3.04 +/- 1.31 using EPI. These differences were not statistically signifcant (P>0.5, t-test). According to the ratio of tumor rCBV/gray matter rCBV, a mean value, 14.5 ml/100 g, of rCBV in meningiomas was calculated. Compared with gray matter, increased inhomogeneous rCBV was observed in meningioma. Based on the two different sequences, no bias can be observed in our rCBV reconstruction.