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Updated: Jun 25, 2026

Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Diagnostic imaging of experimental invasive pulmonary aspergillosis
Thomas J Walsh1, Vidmantas Petraitis, Ruta Petraitiene
1Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. walsht@mail.nih.gov
Abstract:
Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are caused by organism-mediated tissue injury, vascular invasion, and hemorrhagic infarction. Ultrafast computed tomography (UFCT) scanning reproducibly measures these lesions in experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. The pulmonary lesion score from UFCT scanning is a useful outcome variable for measuring differences in efficacy of antifungal compounds alone and in combination, as well as the virulence of different strains and species of Aspergillus. Several studies demonstrate that the course of pulmonary lesions treated with amphotericin B, lipid formulations of amphotericin B, triazoles, echinocandins, and combination therapy measured by serial UFCT scans correlate with those measured by survival, histopathological resolution of lesions, microbiological clearance of Aspergillus fumigatus, and resolution of galactomannan index. We further developed a multidimensional volumetric imaging (MDVI) method for analysis of the volume of pulmonary infiltrates over time in response to antifungal therapy. Volumetric data by MDVI correlate with UFCT pulmonary lesion scores and validated biological endpoints. A recent pilot clinical study demonstrated the applicability of MDVI to human pulmonary fungal infections. MDVI also improves objectivity of radiological assessment of therapeutic response to antifungal therapy and merits more extensive evaluation in patients with invasive aspergillosis, as well as other fungal and bacterial pneumonias.
Insights
Ultrafast computed tomography (UFCT) scanning effectively measures invasive pulmonary aspergillosis lesions in rabbits. This imaging technique, along with multidimensional volumetric imaging (MDVI), aids in assessing antifungal treatment efficacy and disease progression.
Area of Science:
- Medical Imaging
- Mycology
- Pharmacology
Background:
- Invasive aspergillosis in neutropenic hosts causes pulmonary infiltrates via tissue injury and vascular invasion.
- Accurate radiological assessment is crucial for evaluating antifungal therapy effectiveness.
Purpose of the Study:
- To evaluate ultrafast computed tomography (UFCT) scanning for measuring pulmonary lesions in experimental invasive aspergillosis.
- To introduce and validate multidimensional volumetric imaging (MDVI) for assessing antifungal treatment response.
- To correlate imaging findings with established clinical and microbiological endpoints.
Main Methods:
- Experimental invasive pulmonary aspergillosis was established in persistently neutropenic rabbits.
- Lesions were quantified using UFCT scanning and a pulmonary lesion score.
- A novel MDVI method was developed to analyze pulmonary infiltrate volume over time.
- UFCT and MDVI data were correlated with survival, histopathology, and galactomannan index.
Main Results:
- UFCT scanning reproducibly measured pulmonary lesions in experimental aspergillosis.
- The UFCT pulmonary lesion score correlated well with survival, histopathology, and microbiological clearance.
- MDVI volumetric data showed strong correlation with UFCT scores and validated biological endpoints.
- A pilot clinical study indicated MDVI's applicability to human pulmonary fungal infections.
Conclusions:
- UFCT scanning is a valuable tool for assessing invasive pulmonary aspergillosis and antifungal efficacy in preclinical models.
- MDVI offers an objective, volumetric approach to evaluating therapeutic response in pulmonary fungal infections.
- MDVI warrants further investigation in clinical settings for invasive aspergillosis and other pneumonias.
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