Pulmonary Functional Imaging: Basics and Clinical Applications

Foreword
Preface
Contents
Anatomical Basis for Pulmonary Functional Imaging
	1	 Introduction
	2	 Histogenesis
	3	 Lung Parenchyma
		3.1	 Lung Alveoli and Alveolar Ducts
		3.2	 Respiratory Bronchiole
	4	 Lung Interstitium
		4.1	 Pulmonary Vessels
		4.2	 Alveolar Capillary Beds and Venules
		4.3	 Pulmonary Lymphatics
	5	 Pulmonary Secondary Lobules
	6	 Pulmonary Anatomical and Functional Analysis
	7	 Conclusions
	References
Pulmonary Function Tests
	1	 Introduction
	2	 Spirometry
	3	 Lung Volumes
	4	 Diffusing Capacity
		4.1	 Measuring Method
		4.2	 Interpretation of DLCO
	5	 Other Pulmonary Function Tests
		5.1	 Reversibility Test
		5.2	 Bronchoprovocation Test
		5.3	 Arterial Blood Gas Analysis
		5.4	 Respiratory Impedance
		5.5	 Field Walking Tests
		5.6	 Clinical Assessment of Dyspnea
	6	 Summary
	References
Basics and Clinical Application of CT for Pulmonary Functional Evaluation
	1	 Introduction
	2	 Sources of Variation
		2.1	 Radiation Dosage
		2.2	 Iterative Reconstruction Algorithm
	3	 CT Lung Volumetry and Quantitative Parameters
		3.1	 Lung Volume
		3.2	 Lung Densitometric Parameters and Airway Quantification
		3.3	 Pulmonary Vascular Volume
	4	 Dual-Energy Computed Tomography
		4.1	 Lung Perfusion
		4.2	 Lung Ventilation
		4.3	 Lung Ventilation and Perfusion
		4.4	 Thoracic Oncology
	5	 Cine and Four-Dimensional Computed Tomography
	6	 Dynamic Perfusion Computed Tomography Assessment
		6.1	 Dynamic Contrast-Enhanced CT with Perfusion Analyses
		6.2	 Dynamic First-Pass Contrast-Enhanced Perfusion Area-Detector CT
	7	 Conclusion
	References
Basics and Clinical Application of MR Assessment of Pulmonary Hemodynamics and Blood Flow
	1	 Introduction
	2	 Basics
		2.1	 Flow Measurements
			2.1.1	 Prospective and Retrospective Gating Techniques
			2.1.2	 Errors and Limitations
		2.2	 Multidirectional Flow (4D Flow)
		2.3	 Perfusion
		2.4	 Non-contrast-Enhanced Pulmonary Perfusion
		2.5	 Contrast-Enhanced Pulmonary Perfusion
	3	 Clinical Application
		3.1	 2D Flow
		3.2	 4D flow
		3.3	 Perfusion
	References
Basics and Clinical Application of the MR Assessment of Ventilation
	1	 Introduction
	2	 Theory and Rationale of Ventilation Imaging Using MRI
		2.1	 Proton-Based Methods
			2.1.1	 Deformable Image Registration
			2.1.2	 Fourier-Based Methods
			2.1.3	 Oxygen-Enhanced MRI
		2.2	 MR Visible Gas Nuclei
			2.2.1	 Hyperpolarized Gases
			2.2.2	 Perfluorinated Gases
	3	 Clinical Research in Ventilation Imaging Using MRI
		3.1	 Asthma and COPD
		3.2	 Clinical Research Using Dynamic Functional MRI
		3.3	 Pediatric Lung Disease: CF and Asthma
		3.4	 Applications in Lung Cancer
	4	 Summary of Ventilation Imaging Using MRI
	Glossary
	References
Principles and Clinical Applications of Respiratory Motion Assessment Using 4D Computed Tomography and Magnetic Resonance Imaging
	1	 Introduction
	2	 Respiratory Motion Analysis Using MRI
	3	 Method of 4D Dynamic Ventilation MRI
	4	 Method of 4D Dynamic Ventilation CT
	5	 Clinical Application of 4DCT in Large Airways Disorders
	6	 Clinical Application of 4DCT in COPD Patients
	7	 Clinical Application of 4DCT in Patients with Lung Cancer
	8	 The Future of 4D Image Analysis
	9	 Conclusions
	References
Pulmonary Functional Imaging, Basics and Clinical Application of Nuclear Medicine and Hybrid Imaging
	1	 Introduction
	2	 Principles of Measuring Pulmonary Function in Cardiopulmonary Diseases with V/P Spect
		2.1	 Ventilation Scintigraphy
		2.2	 Perfusion Scintigraphy
		2.3	 How to Perform V/P SPECT
			2.3.1	 Image Acquisition
			2.3.2	 Reconstruction
			2.3.3	 Interpretation with Emphasis on PE
			2.3.4	 Recommended Criteria for Reading V/P SPECT with Respect to Acute PE
			2.3.5	 Quantification of PE Extent
			2.3.6	 Follow-Up
		2.4	 Radiation Doses
	3	 Clinical Use of Hybrid V/P SPECT/CT
	4	 Additional Findings
		4.1	 Chronic Obstructive Pulmonary Disease (COPD)
		4.2	 Pneumonia
		4.3	 Left Heart Failure
		4.4	 Preoperative Evaluation of Lung Function
		4.5	 PET and PET/CT or PET/MRI
	5	 Conclusion
	References
Functional Assessment of COPD
	1	 Introduction
	2	 Quantitative Imaging of COPD for Assessment of Pulmonary Function
		2.1	 Emphysema Quantification
		2.2	 Large Airway Measurement: Direct Measurement
		2.3	 Small Airway Measurement: Air-Trapping Measurement
		2.4	 Other Comorbidities of COPD
			2.4.1	 Pulmonary Vascular Change
			2.4.2	 Osteoporosis
			2.4.3	 Diaphragm and Respiratory Muscle
			2.4.4	 Atherosclerosis
	3	 Evaluation of Parenchymal Perfusion and Ventilation
		3.1	 Evaluation of Parenchymal Perfusion
		3.2	 Evaluation of Parenchymal Ventilation
		3.3	 Evaluation of Pulmonary Ventilation, Perfusion and Relationship of Ventilation and Perfusion
	4	 Future Perspectives
	References
Structure-Function Imaging of Asthma: Airway and Ventilation Biomarkers
	1	 Introduction
	2	 Chest Radiography and X-Ray Computed Tomography
		2.1	 Dual-Energy Xenon CT
		2.2	 Challenges
	3	 Optical Coherence Tomography
		3.1	 Challenges
	4	 Positron Emission Tomography
		4.1	 18F-FDG
		4.2	 iNOS
		4.3	 13NN
		4.4	 Challenges
	5	 Magnetic Resonance Imaging
		5.1	 Inhaled Noble Gas MRI
		5.2	 Inhaled Fluorine Gas MRI
		5.3	 Fourier Decomposition 1H MRI (FDMRI)
		5.4	 O2-Enhanced 1H MRI
		5.5	 1H MRI Specific Ventilation
		5.6	 Challenges
	6	 Future Opportunities
	References
Functional Assessment of Cystic Fibrosis Lung Disease
	1	 Introduction
	2	 Computed Tomography
		2.1	 Quantification of Airway Changes
			2.1.1	 Scoring
			2.1.2	 Initial Steps of Software-Based Quantification
			2.1.3	 Use of Quantitative Airway Metrics in CF and Correlation with Pulmonary Function Testing
		2.2	 Imaging of Ventilation and Perfusion with CT
			2.2.1	 Non-Contrast-Dependent Techniques
				2.2.1.1 Mosaicism
				2.2.1.2 Paired Inspiratory-Expiratory Breath-Hold CT
			2.2.2	 Quantitative Post-Processing of Air Trapping
			2.2.3	 Clinical Relevance of Air Trapping
			2.2.4	 Variability of Air Trapping
			2.2.5	 Correlation with Lung Function Testing
			2.2.6	 Correlation with Structural Lung Disease
			2.2.7	 Differentiation of Air Trapping from Emphysema
				2.2.7.1 Other Dynamic Techniques
		2.3	 CT as an Endpoint in Clinical Trials
	3	 Magnetic Resonance Imaging
		3.1	 Quantification of Airway Changes
		3.2	 Imaging of Ventilation and Perfusion with MRI
			3.2.1	 Non-contrast-Dependent Techniques
				3.2.1.1 Mosaicism
				3.2.1.2 Fourier Decomposition MRI and Closely Related Approaches
				3.2.1.3 Arterial Spin Labelling
				3.2.1.4 Phase-Contrast MRI
			3.2.2	 Contrast-Dependent Techniques
				3.2.2.1 Gadolinium-Enhanced 4D Perfusion MRI
				3.2.2.2 Quantification of 4D Perfusion MRI
				3.2.2.3 Variability of Perfusion Abnormalities
				3.2.2.4 Correlation with Structural Lung Disease
				3.2.2.5 Correlation with Pulmonary Function Testing
				3.2.2.6 Gadolinium-Enhanced MR Angiography
				3.2.2.7 Oxygen-Enhanced Ventilation MRI and T1-Mapping
				3.2.2.8 Hyperpolarized Gas Ventilation MRI
		3.3	 MRI as an Endpoint in Clinical Trials
	4	 Conclusion
	References
Functional Assessment of Pulmonary Venous Thromboembolism
	1	 Introduction
	2	 Diagnosis of Pulmonary Thromboembolism
	3	 Assessment of Effects of Acute Pulmonary Thromboembolism
		3.1	 Lung Scintigraphy
			3.1.1	 Positron Emission Tomography
		3.2	 Computed Tomography (CT)
			3.2.1	 Cardiac Assessment and Right Heart Strain
			3.2.2	 Pulmonary Perfusion
		3.3	 Magnetic Resonance Imaging (MRI)
			3.3.1	 Cardiac Assessment and Right Heart Strain
			3.3.2	 Pulmonary Perfusion
	4	 Diagnosis of Chronic Pulmonary Thromboembolism
		4.1	 CT Assessment of Chronic Thromboembolic Disease
		4.2	 MR Imaging of Chronic Thromboembolic Disease
	5	 Conclusions
	References
Multimodality Imaging of Pulmonary Hypertension: Prognostication of Therapeutic Outcomes
	1	 Introduction
	2	 Cardiovascular Consequences of Pulmonary Hypertension
	3	 Evaluation of the Right Ventricle
		3.1	 Non-contrast Computed Tomography
		3.2	 Contrast-Enhanced Computed Tomography
		3.3	 Cardiac-Gated Computed Tomographic Angiography
	4	 MRI
	5	 Evaluation of the Interventricular Septum
	6	 Evaluation of Additional Cardiac Chambers
	7	 Evaluation of the Vasculature
	8	 Ratio of the Pulmonary to Systemic Blood Flow
	9	 Pulmonary and Tricuspid Valve Regurgitation and Jet Velocity
	10	 Mediastinal Diseases
	11	 Diseases of the Left Heart
	12	 Diastolic Dysfunction
	13	 Mitral Valve Disease
	14	 Aortic Valve Disease
	15	 Left Main Coronary artery Compression by the Pulmonary Artery
	16	 Four-Dimensional Phase-Contrast Flow-Encoded Magnetic Resonance Angiography (4D Flow MRI)
	17	 Lung Parenchymal Disease
	18	 Liver Disease
	19	 Obstructive Sleep Apnea
	20	 Synergy of Diseases
	21	 Modeling the Severity of Pulmonary Hypertension Using MRI Parameters
	22	 Prediction of Outcomes After Therapy for Pulmonary Hypertension
	23	 Noninvasive Imaging Costs
	24	 Conclusion
	References
Functional Assessment of Lung Cancer and Nodules
	1	 Introduction
	2	 Prediction of Postoperative Lung Function of Lung Cancer Candidates for Surgical Treatment
		2.1	 Current Guideline-Based Radiological Examination for Prediction of Postoperative Lung Function of Lung Cancer Candidates for Surgical Resection
		2.2	 Prediction of Postoperative Lung Function Using SPECT and SPECT/CT
		2.3	 Prediction of Postoperative Lung Function Using MR Imaging with Different Methods
		2.4	 Prediction of Postoperative Lung Function Using Dual-Energy CT with Perfusion and Ventilation Assessments
	3	 Pulmonary Functional Imaging for Differentiating Malignant from Benign Lesions
		3.1	 Background for Contrast Enhancement
			3.1.1	 Pathological Background
			3.1.2	 Pharmacokinetic Background
				3.1.2.1 Normal Lung Tissue
				3.1.2.2 Malignant and Benign Lesions
				3.1.2.3 Inflammatory Lesions with High- and Low-Level Biological Activity
		3.2	 Dynamic CE-CT and Dynamic CE-MR Imaging Without Ultra-Short TE
		3.3	 3D Dynamic First-Pass Contrast-Enhanced MR Imaging with Ultra-Short TE Equal to or Less Than 2.0 ms
		3.4	 Dynamic First-Pass CE-Perfusion CT Using Multidetector-Row and Area-Detector CT Systems
	4	 Prediction of Treatment Outcome and Recurrence for Lung Cancer Patients Treated with Conservative Therapy
		4.1	 Dynamic CE-MR Imaging with Ultra-Short TE Equal to or Less Than 2.0 ms
		4.2	 Dynamic First-Pass CE-Perfusion CT and ADCT
	5	 Conclusion
	References
Computational Approach toward Pulmonary Functional Imaging
	1	 Quantitative Measurement of Lung Function: Metrics and Modalities
		1.1	 Introduction
		1.2	 Measuring Ventilation
		1.3	 Measuring Perfusion
		1.4	 Measuring Respiratory Motion
	2	 Computational Lung Image Analysis
		2.1	 Introduction
		2.2	 Image Registration
		2.3	 Image Segmentation
	3	 Computational Functional Biomarkers of Lung Diseases
		3.1	 Introduction
		3.2	 Asthma
		3.3	 COPD
		3.4	 Cystic Fibrosis
		3.5	 Pulmonary Embolism
	4	 Efforts Toward Automated Diagnosis and Prognosis of Lung Disease
		4.1	 Introduction
		4.2	 Prediction of Disease Progression in COPD Patients
		4.3	 Predicting Malignancy of Pulmonary Nodules
		4.4	 Predicting Need for Lung Transplant in Cystic Fibrosis Patients
	5	 Summary
	References
Image-Based Phenotyping, Deep Learning (DL), and Artificial Intelligence (AI) Applications in Clinical and Research Radiology and Chest Imaging
	1	 Image-Based Phenotyping
		1.1	 Figures (Two Figures from Radiology 2018 with Permission)
	2	 Deep Learning (DL) and Artificial Intelligence (AI) Applications in Clinical and Research Radiology
		2.1	 Availability of Large, Annotated Sets of Labeled Data for Training and Testing
		2.2	 Deep Learning Algorithms Need Real-World Testing
		2.3	 Black-Box Nature: Why Do DL NNs Work?
		2.4	 Interpretation: Develop and Implement Algorithms that Self-Explain themselves
	3	 Current Application of Deep Learning in Chest Imaging
		3.1	 Chest Radiography
		3.2	 Computed Tomography
	4	 Conclusion
	References
Future of Pulmonary Functional Imaging
	1	 Introduction
	2	 Ventilation Imaging
		2.1	 Nuclear Medicine Examination
		2.2	 Hyperpolarized Noble Gas MR Imaging
		2.3	 Fluorinated Gas MR Imaging
		2.4	 Oxygen-Enhanced MR Imaging
		2.5	 Xenon-Enhanced Ventilation CT
	3	 Perfusion Imaging
		3.1	 Nuclear Medicine Examination
		3.2	 Non-Contrast-Enhanced and Contrast-Enhanced MR Angiography and Perfusion MR Imaging
		3.3	 CE-Multi-Energy CT for Pulmonary Perfusion Assessment
		3.4	 Dynamic First-Pass CE-Perfusion Area-Detector CT (ADCT)
		3.5	 Pulmonary Hemodynamic Evaluation by Phase-Contrast MR Imaging
	4	 Biomechanics Evaluation as Pulmonary Functional Imaging
		4.1	 CT-Based Biomechanics Assessment
		4.2	 MR-Based Biomechanics Assessment
	5	 Challenges of New Methods for Future Pulmonary Functional Imaging
	6	 Conclusion
	References