Multimodal MRI Study Of Brain Structure And Function In Patients With COPD

COPD?Chronic obstructive pulmanory diseas?is a complex multicomponent disorder that is related to an extensive variety of comorbidities.Cognitive impairment is one of the most frequent extrapulmonary manifestations in COPD patients,and it has been associated with higher mortality and disability.Although the underlying mechanisms remain poorly understood.However,the potential role of hypoxia in triggering cranial neuronal damage and dysfunction has often been hypothesized.More sensitive and quantitative functional MRI techniques can reveal the change of microstructure that assesses functional abnormality in a macroscopic normal brain.This study is based on multimodal functional magnetic resonance technology and is divided into four parts,combining COPD brain structure,function and clinical datathrough the information complementation between different modal data.The aim of this study is to search for COPD brain function-specific imaging biomarkers and provide a new theoretical basis for revealing the neuropsychological mechanism of COPD.Part I:Mild Cognitive impairment and clinical characteristics in patients with COPDPurpose:To investigate the prevalence of MCI and domain-specific cognitive impairment of COPD by using MoCA questionnaire,and to evaluate the relationship between MoCA scores and pulmonary function,arterial blood gas analysis in COPD.Materials and Methods:We enrolled 72 stable patients with COPD and 55 control subjects with matched sex,age,education level,and body mass index?BMI?.cognitive function was assessed for all subjects by using the Montreal Cognitive Assessment?MoCA?,and the comparison of MoCA total scores and visual space and executive function,naming,memory,attention,language,abstraction,delayed recall,orientation between the two groups were performed.Multiple regression analyses were performed to evaluate the relationship between the indices and cognitive function in the COPD group.Results:Total of sixty COPD and fourty-eight HC subjects were included into the final analyses.The MoCA scores of the COPD group was significantly lower than the HC group?P<0.05?.The main impaired cognitive domains in the COPD group were visual space and executive function,naming,attention,and abstraction.The MoCA scores of COPD group was positively correlated with SaO₂ and PaO₂,and negatively correlated with PaCO₂?P<0.05?.Conclusion:Patients with stable COPD have mild cognitive impairement,mainly in visual space and executive function,naming,attention,abstract cognitive domain,Moreover,cognitive impairement is associated with arterial blood gases.Part II:Evaluation of gray matter volume in patients with COPD based on voxel-based morphological analysisPrepose:Grey matter?GM?volume changes in patients with COPD were evaluated using voxel-based morphological analysis?VBM?.Materials and Methods:Sixty patients with COPD?42 males,18 females,32 moderate COPD patients,28 severe COPD patients?,and 48 control subjects?35 males and 13 females?were enrolled into this study.The data of arterial blood gas,lung function and cognitive function were acquired for all subjects.All subjects underwent high-resolution 3D T1WI structures MR scanning.Differences in gray matter volume between the two groups were analyzed using VBM software.Results:Total of fourty COPD and fourty HC subjects were included into the final analyses.Compared to controls,patients with COPD showed decreased GM volume in thebilateral middle temporal gyrus,right occipital gyrus,right inferior frontal gyrus,bilateral marginal superior gyrus,left frontal median/superior gyrus,left central anterior gyrus,left precuneus.The brain volume with increased GM located in the bilateral striatum.The MoCA score of COPD group was significantly lower than that of HC group,and the difference of visual space and executive function,attention,abstraction and delayed memory score was statistically significant?P<0.05?.In COPD,the volume decrease in the left frontal gyrus was positively correlated with FVC?r=0.348,P=0.028?and negatively correlated with FEV₁/FVC?r=-0.350,P=0.027?,the volume decrease in the right frontal gyrus was negatively correlated with SaO₂ and PaO₂?r=-0.384 P=0.014,r=-0.350 P=0.027?,the volume decrease in the right inferior frontal gyrus was negatively correlated with language score?r=-0.317 P=0.046,r=-0.346 P=0.029?,The volume increase in the right striatum was positively correlated with the predicted value of FEV₁%and the predicted value of FVC%?r=0.312 P=0.050,r=0.389 P=0.013?,the volume decrease in the right superior margin was positively correlated with FEV₁?r=0.326,P=0.040?.The volume decreasein the left frontal gyrus was positively correlated with FVC?r=0.358,P=0.023?,and positively correlated with FEV₁/FVC?r=-0.334,P=0.035?,The volume decrease in the left superior margin was negatively correlated with SaO₂ and PaO₂?r=-0.439 P=0.005,r=-0.385 P=0.014?,and negatively correlated with delayed memory score?r=-0.321,P=0.044?,The volume decrease in the central anterior gyrus was negatively correlated with SaO₂ and PaO₂?r=-0.406P=0.009,r=-0.399 P=0.011?,and positively correlated with PaCO₂ and FVC?r=-0.324P=0.041,r=-0.318 P=0.045?,negatively correlated with language score?r=-0.372,P=0.018?.Conclusion:Abnormalities of GM volume in various brain regions were found in stable COPD,and volume changes of several brain regions were associated with lung function,arterial blood gas analysis,and neurocognitive scores.These findings may provide new insights into the pathogenesis of COPD.Part III:Resting-state fMRI study on Cerebral perfusion,spontaneous brain activity and functional connectivity in patients with COPD1.Evaluation of cerebral perfusion changes in patients with COPD by using 3D-ASLPurpose:To detect the changes of cerebral perfusion in patients with COPD),and to evaluate the relationship between cerebral blood flow?CBF?and arterial blood gas analysis,pulmonary function test,neurocognitive function.Materials and methods:40 patients with COPD and 40 healthy controls underwent a whole-brain 3D pseudo-continuous arterial spin labeling?3D pc-ASL?magnetic resonance?MR?examination.The data of arterial blood gas,lung function and cognitive function were acquired for all subjects.The voxel-level CBF values of the whole brain were compared between the two groups by using the SPM software.Further analysis of the correlation between CBF and pulmonary function,arterial blood gas analysis,neurocognitive scores were performed in patients with COPD.Result:The visual space and executive function,attention,abstraction,and delayed memory scores in COPD group were significantly lower than the control group?P<0.001?.The mean CBF of whole brain?41.40±9.71 mL/100 g/min:46.15±7.91 mL/100 g/min?,gray matter?43.91±10.67 mL/100 g/min:49.34±9.13 mL/100 g/min?and white matter?38.34±8.70mL/100 g/min:42.51±6.29 mL/100 g/min?in COPD group was lower than that of the control group.Compared to HC,COPD group showed decreased CBF in right frontal middle gyrus,right lower lobule and right striatum?P<0.05?.In COPD,the CBF of the right striatum and right subapical lobule were positively correlated with PaCO₂?r=0.413 P=0.008,r=0.397 P=0.011??Conclusion:The study demonstrated a potential relationship between abnormalities of cerebral perfusion and cognitive impairment in patients with COPD.PaCO₂ may be a factor that affects the reduction of CBF in the right frontal gyrus,right inferior parietal lobeand right striatum.3D pc-ASL technique could non-invasively provide valuable cerebral perfusion information for the further neuropsychological study in COPD.2.Alteration of spontaneous brain activity in COPD patients:resting-state fMRI studyPurpose:To detect spontaneous brain activity in patients with COPD,and to evaluate the correlation between spontaneous brain activity and clinical data.Materials and Methods:The clinical data and fMRI data of 40 patients in the COPD group and 40 control group were taken from the second and third parts.ALFF values were calculated by using DPARSF software.Two sample t-test was performed to analyze differences between the two groups.The correlation between ALFF and lung function,arterial blood gas analysis,and MoCA score was further analysed by using Pearson's correlation analysis.Results:Compared to the control group,Patients with COPD showed increased ALFF in the right medial frontal gyrus,left superior frontal gyrus,bilateral middle occipital gyrus,right middle temporal gyrus,left medial frontal gyrus,left subapical lobule.The ALFF value of the right medial frontal gyrus was negatively correlated with PaO₂ and FEV₁/FVC?r=-0.323 P=0.042,r=-0.417 P=0.007?,and positively correlated with PaCO₂?r=0.472,P=0.002?,negative correlation with MoCA score?r=-0.323,P=0.042??attention:r=-0.342 P=0.031,language:r=-0.343 P=0.030,delayed recall:r=-0.327,P=0.039,orientation:r=-0.434,P=0.005?.The ALFF value of the left superior frontal gyrus was negatively correlated with PaO₂?r=-0.344,P=0.030?and positively correlated with PaCO₂?r=0.478,P=0.002?.The ALFF value of the right middle occipital gyrus was negatively correlated with FEV₁/FVC?r=-0.440,P=0.004?,and orientation score?r=-0.357,P=0.024?.The ALFF value of the right middle temporal gyrus was negatively correlated with FEV₁/FVC,attention score,and orientation score?r=-0.335 P=0.035,r=-0.312 P=0.050,r=-0.402,P=0.010?.The left medial frontal gyrus ALFF value was negatively correlated with FEV₁%predicted value,FEV₁/FVC,and attention score?r=-0.361 P=0.022,r=-0.344 P=0.030,r=-0.390 P=0.013,r=-0.323 P=0.042?,and positively correlated with PaCO₂?r=0.391,P=0.013?.The ALFF value of the left middle occipital gyrus was negatively correlated with PaO₂ and FEV₁/FVC?r=-0.323 P=0.042,r=-0.520 P=0.001?,and negatively correlated with MoCA score?r=-0.386,P=0.014??attention:r=-0.379 P=0.016,naming:r=-0.355 P=0.024,delayed recall:r=-0.337 P=0.034,orientation:r=-0.449 P=0.004?.The ALFF value of the left subapical lobule was negatively correlated with FEV₁/FVC and directional score?r=-0.326 P=0.040,r=-0.328 P=0.039?.Conclusion:COPD patients showed abnormal brain activity in multiple brain regions during resting state,reflecting the potential pathophysiological mechanism of cognitive impairment,and providing valuable information for further study on brain function of COPD.3.Altered seed-based resting-state function connectivity in COPD patientsPurpose:A seed-based approach was used to study the resting-state function connectivity in patients with COPD,and to evaluate the relationship between function connectivity and clinical data.Materials and Methods:40 patients with COPD and 40 control subjects were performed BOLD sequence scanning.The brain region with abnormal volume were defined as the seeds.REST software was used to calculate the function connectivity?FC?between the seeds and the whole brain,and the FC differences between the two groups were analyzed.Pearson correlation was used to analyze the relationship between FC values and lung function,arterial blood gas analysis,and neurocognitive scores.Results:Compared to control group,patients with COPD showed significantly decreased rs-FC between the left middle temporal gyrus and left middle frontal gyrus,right middle occipital gyrus and left striatum,right striatum and the left striatum?all P<0.05?.The rs-FC between the left middle temporal gyrus and left middle frontal gyrus were positively correlated with orientation scores?r=0.353,P=0.026?.The rs-FC between the left middle temporal gyrus and left middle frontal gyrus were positively correlated with orientation score?r=0.353,P=0.026?,and the rs-FC between the right striatum and left striatumwere positively correlated with naming and abstract score?r=0.326,P=0.040,r=0.361 P=0.022?.Conclusion:Based on the seeds,this study revealed the abnormal rs-FC within the left middle temporal gyrus,left medial frontal gyrus,right middle occipital gyrus,and bilateral striatum in patients with COPD.These results contribute to better understanding of how abnormal function connectivity in the brain regions of COPD patients affect cognitive function.Part IV Multi-parameter coupling of fMRI technology foranalysis of structure and function of patients with COPDPurpose:Coupling multiple fMRI parameters to evaluate the relationship between brain structure and function changes and neurocognition in patients with COPD.Materials and Methods:The clinical data and fMRI data of 40 patients with COPD and40 controls were the same as the second and third parts.Brain regions with abnormal gray matter volumewere defined as ROI and saved as masks in REST software.The average value of ALFF,CBF and volume were extracted.Pearson correlation was used to analyze the relationship between structural and functional data in the two groupsResults:In the HC group,the ALFF-CBF in right middle occipital gyrus,right middle temporal gyrus and right upper marginal gyrus showed positive correlationsd?r=0.675,P=0.004;r=0.520,P=0.039;r=0.562 P=0.023?.And positive correlation were found in ALFF-CBF,ALFF-VBM and CBF-Volume in the right striatum and the left superior marginal gyrus?r=0.531,P=0.034;r=0.726,P=0.001;r=0.501,P=0.048;r=0.543,P=0.030;r=0.499,P=0.049;r=0.795,P<0.001?.The ALFF-CBF and ALFF-VBM coupling in the left striatum showed positive correlations?r=0.664,P=0.005;r=0.663,P=0.005?.The ALFF-CBF,ALFF-VBM,and CBF-VBM coupling in the left central anterior gyrus showed positive correlation?r=0.422,P=0.007;r=0.378,P=0.016;r=0.420,P=0.007?.The CBF-VBM coupling in the left medial frontal gyrus showed positive correlations?r=0.729,P=0.001?.Interestingly,there was no significant correlation in ALFF-CBF,ALFF-VBM and CBF-Volume in the 11 different brain regions in the COPD group?all P>0.05?.Conclusion:The fMRI multi-parameter coupling technique combines brain fMRI imaging features and clinical information from multiple perspectives.Through information complementation,this study deepened the understanding of the neurophysiological mechanisms of COPD.