title: Diagnostic imaging of experimental invasive pulmonary aspergillosis.
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.
authors.affiliation: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. walsht@mail.nih.gov
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: Vidmantas
authors.initials: V
authors.lastname: Petraitis
authors.forename: Ruta
authors.initials: R
authors.lastname: Petraitiene
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Solomon
authors.forename: John D
authors.initials: JD
authors.lastname: Bacher
authors.forename: Lora
authors.initials: L
authors.lastname: Greene
authors.forename: Margaret
authors.initials: M
authors.lastname: Cotton
authors.forename: Andreas
authors.initials: A
authors.lastname: Groll
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Roilides
authors.forename: Nilo
authors.initials: N
authors.lastname: Avila
authors.forename: Vasilios
authors.initials: V
authors.lastname: Pyrgos
authors.forename: Shmuel
authors.initials: S
authors.lastname: Shoham
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D001232:Aspergillus fumigatus / Q000302:isolation & purification; D003952:Diagnostic Imaging; D016903:Drug Monitoring; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis* / Q000188:drug therapy; D008137:Longitudinal Studies; D011817:Rabbits; D013902:Radiography, Thoracic; D014054:Tomography
chemical_list: D000935:Antifungal Agents