A crazy paving pattern is diagnosed and detected on High-resolution Computed tomography (HRCT). The resolution for HRCT allows the characterization of the changes at the level of the secondary pulmonary lobule. In several cases, the disease processes may be indistinguishable however, clinical presentation and subtle imaging pointers may allow us to make the appropriate diagnosis. We may subdivide the causes into acute or chronic or alveolar or interstitial predominant components. We present illustrative cases of a few of the important causes as follows:

1. Pulmonary edema: It is characterized by the extracellular movement of fluid into the alveolar spaces and interstitium. It occurs due to an imbalance between the hydrostatic and oncotic pressure. Radiological findings include cardiomegaly with bilateral pleural effusions and smooth septal thickening in the background of diffuse ground glass opacity giving rise to the classical pattern.[2]
   

   Fig 1: Bilateral perihilar (peripheries spared) diffuse symmetric ground glass opacity with smooth septa thickening is seen (Panel A- axial lung window section). On the mediastinal window (Panel B) bilateral mild pleural effusion is seen with cardiomegaly. The magnified image (Panel C) shows the typical crazy paving pattern in the right upper lobe. Coronal reformat images (Panel D) show significant cardiomegaly. These findings are typical and almost pathognomonic for pulmonary edema.
   . Adult respiratory distress syndrome which is characterized by hypoxia with edema in the lung parenchyma is due to various noncardiogenic causes including trauma, toxin-related, or sepsis and is usually not associated with cardiomegaly.
2. Toxic pulmonary hemorrhage: Inhalational use of recreational drugs can lead to lung parenchymal injury sometimes referred to as “crack lung” in cases of cocaine abuse. Ground glass opacities, smooth septal thickening, and crazy paving pattern may be recognized as imaging findings. However, this diagnosis requires detailed clinical evaluation, history taking, and temporal association with recreational drug use/ drug abuse.[3,4] An illustrative case of a young male with a history of recreational drug use.
   

   Fig 2: A 22-year-old male was found unconscious with severe hypoxia and subsequently mechanically ventilated. HRCT was performed in the emergency settings after stabilization which revealed bilateral perihilar and central symmetric areas of crazy paving in both lungs (Panel A- axial lung window sections) and better visualized on the magnified image(Panel B). Pneumomediastinum likely barotrauma-associated is seen (Panel A, C) Bilateral and central pattern are better appreciated on coronal lung window images(Panel D). On bronchoalveolar lavage, bloody aspirate was found. On further evaluation, a history of recreational drug inhalations(cocaine) was elicited, and a provisional diagnosis of toxic pulmonary hemorrhage syndrome was made.
3. Vasculitis Syndromes: Small vessel ANCA-associated vasculitides(primary) which include granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic polyangiitis are most commonly associated with pulmonary involvement. Clinically multisystem involvement, especially renal, pulmonary, and sino-nasal involvement may suggest a complete immunological lab workup. Pulmonary imaging findings can include single or multiple solid/cavitating nodules, multifocal ground glass opacities, crazy paving pattern as well as consolidations are also described. [5]
   

   Fig 3: A female patient presented with hemoptysis, she underwent a chest radiography which revealed areas of hazy air space opacity(not shown). She underwent a noncontrast HRCT chest which showed patchy areas of ground glass opacity with interlobular septal thickening (Panel A). The magnified image (Panel B) shows patchy areas of crazy paving appearance. Parenchymal changes are seen predominantly in the central regions and asymmetrically in both lungs(Panel C, D – sagittal and coronal reformats). Clinically she also had polyarthritis and laboratory parameters for the patient revealed elevated Anti-MPO antibodies >200 and deranged renal function tests. Hence, a diagnosis of microscopic polyangiitis was considered.
4. Pulmonary alveolar proteinosis: It is a rare disorder characterized by the deposition of PAS-positive proteinaceous substance in the alveoli. Whole lung lavage had traditionally provided relief and a therapeutic option. The natural history of patients with PAP can be variable, with spontaneous resolution, progression to interstitial fibrosis, and a relatively stable course. Recently exogenous granulocyte-macrophage colony stimulating factor(GM-CSF) has been used for treatment. There has been a suggestion of the role of inhaled recombinant GM-CSF(Molgramostim) in patients who demonstrate autoantibodies to GM CSF-autoimmune PAP. Our patient demonstrated anti-GM CSF antibodies and he was provided the above-mentioned therapy, showing clinical and radiological improvement.[6,7]
   

   Fig 4: A 57-year-old man presented with progressive breathlessness and his CT chest(Panel A, B, C) revealed bilateral asymmetric areas of crazy paving seen with no central/peripheral predilection. Bronchoalveolar lavage was formed which revealed a cloudy aspirate that cleared over time and the number of lavage. A diagnosis of pulmonary alveolar proteinosis was made. He also tested positive for anti-GMCSF antibodies and hence was also treated with Molgramostim which showed significant clearing over 6 months.
5. Drug-induced pulmonary injury: With the advent of newer immunomodulators and chemotherapy drugs, medication-induced lung injury is an increasingly challenging diagnostic entity. Diffuse alveolar damage is the most common type of drug-induced lung injury pattern with a predominant ground glass opacity component. Patchy areas showing crazy paving pattern can be visualized due to the involvement/injury of both alveolar and interstitial components. Temporal association of drug intake is essential to make a diagnosis. [8]
   

   Fig 5: Patchy areas of ground glass opacity with associated interlobular septal thickening asymmetrically in both lungs, with subtle lower lobe predominance (Panel A, B- axial lung window sections) are seen in a patient suffering from lung Non-small cell lung carcinoma and presenting with worsening dyspnea. Panel C shows these multifocal patchy areas of crazy paving are seen in peri-broncho-vascular and subpleural locations. Panel D shows the right upper lobar mass with spiculate margins consistent with the primary tumor. She was being treated with Nivolumab last year, which has been attributed to causing these lung parenchymal changes.
6. Infections due to atypical organisms: Atypical pulmonary infections are seen in predisposed individuals due to significant systemic immunosuppression which may be due to high doses of corticosteroids, or HIV infection to name a few. These atypical organisms include viral organisms, Pneumocystis carnii. Ground glass opacities with mild septal thickening can be seen in nearly all viral pneumonia, however, minor differences are seen in distributions and the presence of additional findings. It may not be possible to differentiate various types based on only radiology, yet important clues can be suggested. Illustrative examples of pneumocystis carnii pneumonia, herpes simplex viral pneumonitis, and COVID-19 pneumonia have been provided.[9,10]
   

   Fig 6: A 48-year-old male patient, diagnosed case of juvenile arthritis adult type being treated with immunosuppressants which include corticosteroids, cyclophosphamide, and rituximab over the last 2 years, presented with acute onset dyspnea and the chest radiograph appeared normal(not shown). He underwent an HRCT chest which revealed bilateral symmetric, perihilar areas of ground glass opacity(Panel A) with interlobular and intralobular septal thickening (more conspicuous in Panel B). Coronal reformat images (Panel C) show a symmetric pattern, in this case upper lobe predominant. In view of immunosuppression, the possibility of atypical infection was considered which was later confirmed on the microbiological workup in form of sputum positivity for Pneumocystis carnii.
   

   Fig 7: Diffuse bilateral ground glass opacities with few areas showing interlobular septal thickening in both lungs (Panel A, B- axial lung window sections) in a patient presenting with dry cough for 1 year. He complained of worsening for the last 3 weeks with a productive cough and worsening breathlessness. The coronal lung window reformat (Panel C) shows areas giving rise to crazy paving pattern. It is well visualized in the right lower lobe(Panel D – sagittal lung window reformat). Lab studies revealed he was seropositive for HIV as well as showed high titers for herpes simplex virus. He worsened, and was shifted to ECMO due to worsening condition due to the viral pneumonia.
   

   Fig 8: Patchy bilateral ground glass opacities with interlobular septal thickening in both lungs (Panel A, B- axial lung window sections) in a patient presenting with dry cough for 1 year. The patient complained of fever, anosmia, and breathlessness with worsening over the last 1 week. The coronal lung window reformat (Panel C) shows areas giving rise to the crazy paving pattern. It is well visualized in the left upper lobe(Panel D – sagittal lung window reformat). Lab studies revealed a positive RT PCR for the COVID-19 virus. These imaging findings are consistent with patterns described for COVID-19 pneumonia
   .
7. Lepidic pattern of primary lung malignancy: Bronchioalveolar carcinoma is the most common malignancy to present with crazy paving pattern on imaging, however, cases of squamous cell carcinoma presenting with the same have been reported. The involvement may be unilateral or bilateral, bilateral involvement has been seen more commonly with bronchioalveolar carcinoma. Lepidic spread of malignant cells is the underlying pathogenesis. [11,12]We share a case of pulmonary adenocarcinoma which shows a multifocal crazy paving pattern.
   

   Fig 9: Bilateral multifocal right upper lobar predominant area of crazy paving is visualized(Panel A – axial lung window sections) with associated ipsilateral hilar lymphadenopathy(Panel B- axial mediastinal window post-contrast CT images). On the magnified image(Panel C), interlobular septal thickening with background subtle ground glass opacity is well visualized. On transbronchial sampling, the lepidic growth pattern of primary lung adenocarcinoma was confirmed as etiology.
8. Lymphangitis carcinomatosa: When there is a spread of carcinomatous cells from the primary lung tumor via the pulmonary interstitial lymphatics, it is termed lymphangitis carcinomatosa. It represents a poor prognostic imaging marker and is characterized by thick nodular asymmetric interlobular septal thickening in the lung parenchyma which is adjacent and contiguous with the primary lung tumor in late stages. We share a case where we can appreciate these imaging findings.[13]
   

   Fig 10: In a known case of primary lung adenocarcinoma in the left upper lobe, on contrast enhanced soft tissue window (Panel A), heterogeneously enhancing soft tissue seen in the left upper lobe. There is irregular nodular septal thickening and subtle background ground glass opacity in the adjacent and contiguous lung parenchyma of the left upper lobe(Panel B), lingula(Panel C), and left lower lobe (Panel D). This imaging finding is consistent with the lymphangitic spread of malignancy into the adjacent lung parenchyma via peri-lymphatic route.
9. Graft vs host disease: This entity is seen after hematopoietic stem cell transplant most commonly and can be difficult to differentiate from acute infections in the early phase. There are diffuse bilateral ground glass opacities seen as compared to patchy which are more commonly seen in infection. It may be acute or chronic, depending on the mechanisms and time of onset following the transplant. Acute GVHD on average presents after 5 months, with frequent involvement of the skin, and gastrointestinal tract. On imaging ground glass opacity, fibrosis, and cysts may be seen. Chronic GVHD presents with consolidations showing organizing pneumonia pattern or bronchiolitis obliterans pattern showing mosaic attenuation, air trapping, and nodules. [14,15]An illustrative case of graft versus host disease has been shared to underline the findings.
   

   Fig 11: A 53-year-old man underwent a familial allogeneic hematopoietic transplant in 2014, after which he developed thrombocytopenia and altered as well as fresh blood in stools(over months) which clinically suggested intestinal graft versus host disease. He developed difficulty in breathing insidiously over time (by 2016). HRCT performed revealed diffuse asymmetric bilateral ground glass opacity with septal thickening and air-filled cystic structures (Panel A, D – axial lung window section). Diffuse involvement with predominance in peri-broncho-vascular locations is visualized on the sagittal and coronal reformats. (Panel B, C). A possibility of pulmonary graft versus host disease was considered in view of therapeutic response to sirolimus and high-dose corticosteroids.
10. Pulmonary lymphangiomatosis: A multisystem disease characterized by proliferation and dilation of lymphatics. The later presentation is attributed to hormonal stimulation. Despite a benign entity, it may be locally aggressive and cause progressive dyspnea and death. Bilateral diffuse upper lobe predominant interstitial septal and peri-bronchovascular thickening, which may be nodular. Ground glass opacity seen may be due to edema or hemorrhage. Lymphatic proliferation can also be visualized in mediastinum without any mass effects on the structures. However, no significant lymphadenopathy is seen.[16] We present a case of this rare disease with typical findings.
    

    Fig 12: Histopathologically proven case of pulmonary lymphangiomatosis. Panel A shows ground glass opacity with irregular septal thickening. Diffuse bilateral peri broncho vascular thickening is seen in Panel B. Coronal reformat images in Panel C show the crazy paving appearance. Panels D, E, and F show hypodense sheet-like tissue in the mediastinum suggestive of lymphatic proliferation with no mass effect. Magnified lung window images in panel G show peri-broncho vascular thickening and interstitial septal thickening.
11. Interstitial lung disease: Crazy paving pattern has been described for multiple interstitial lung diseases which includes hypersensitivity pneumonitis(HP), non-specific interstitial pneumonia(NSIP), Usual interstitial pneumonia(UIP) as well as sarcoidosis. The fibrous thickening of the interstitial septae leads to intralobular and interobular septal thickenings with alveolar inflammatory exudates causing ground glass opacity and creating the crazy paving pattern.[1] Our case, diagnosed with sarcoidosis and Idiopathic Pulmonary Fibrosis demonstrates these findings.
    

    Fig 13: A 50-year-old male patient, who has been diagnosed with a combination of sarcoidosis and idiopathic pulmonary fibrosis previously and is being treated with anti-fibrotics and steroids, presented with acute breathlessness. HRCT chest shows lower lobe posterior predominant ground glass opacity with interlobular septal thickening(Panels A, B, and C show craniocaudal sequential axial lung window sections). Sagittal reformats(Panel E) and Coronal reformats (Panel F) show bilateral relatively symmetric involvement with suggestion of bronchiolectasis as well consistent with fibrosing interstitial lung disease pattern.
12. Alveolar microlithiasis: A rare disorder incidentally detected, characterized by deposition of hydroxyapatite microliths in alveoli. It is a hereditary disease, and though detected incidentally, it progresses slowly over decades and causes respiratory insufficiency. Due to the deposition of these tiny(<3mm sized) microliths within the alveoli, an inflammatory response is elicited which causes ground glass opacity and may be associated with interstitial septal thickening. Crazy paving may be seen, however, the thickened septae show linear hyperdensity along these septae which differentiates it from PAP.[17] We present images of a patient with a lung window showing wider window settings to better appreciate the hyperdensity along with the pulmonary findings.
    

    Fig 14: On the axial-specific lung window settings, a bilateral crazy paving pattern with well-visualized inter and intralobular septal thickening is seen (Panel A). Bilateral diffuse pattern with no peripheral sparing is well visualized in coronal and sagittal reformats (Panel B, C). On these non-contrast images (Panel D), this septal thickening is hyperdense and suggests calcifications. These are the typical findings for microlithiasis.