Aspergillus infection monitored by multimodal imaging in a rat model

Abstract

Although myriads of experimental approaches have been published in the field of fungal infection diagnostics, interestingly, in 21st century there is no satisfactory early noninvasive tool for Aspergillus diagnostics with good sensitivity and specificity. In this work, we for the first time described the fungal burden in rat lungs by multimodal imaging approach. The Aspergillus infection was monitored by positron emission tomography and light microscopy employing modified Grocott's methenamine silver staining and eosin counterstaining. Laser ablation inductively coupled plasma mass spectrometry imaging has revealed a dramatic iron increase in fungi-affected areas, which can be presumably attributed to microbial siderophores. Quantitative elemental data were inferred from matrix-matched standards prepared from rat lungs. The iron, silver, and gold MS images collected with variable laser foci revealed that particularly silver or gold can be used as excellent elements useful for sensitively tracking the Aspergillus infection. The limit of detection was determined for both (107) Ag and (197) Au as 0.03 μg/g (5 μm laser focus). The selective incorporation of (107) Ag and (197) Au into fungal cell bodies and low background noise from both elements were confirmed by energy dispersive X-ray scattering utilizing the submicron lateral resolving power of scanning electron microscopy. The low limits of detection and quantitation of both gold and silver make ICP-MS imaging monitoring a viable alternative to standard optical evaluation used in current clinical settings.

Siderophores for molecular imaging applications

“…non-specific infection and inflammation PET imaging agent) was also found [51]. High contrast imaging of A. f. pulmonary infection in a rat model was achieved using micro-PET/CT technology [50,52], exhibiting pronounced accumulation of 68 Ga-TAFC in infected areas extremely early after onset of infection, which increased with severity of infection and correlated with abnormal CT images (Fig. 4).…”

Meet interesting abbreviations in clinical mass spectrometry: from compound classification by REIMS to multimodal and mass spectrometry imaging (MSI)

“…Although the data show that 1% formaldehyde concentration could be enough, one has to be aware about an increased infectivity occuring during the microorganism passage throughout a host. In our model of experimental aspergillosis in rats (Pluhacek et al, 2016), we noticed that for the full inactivation of A. fumigatus isolated from lungs of infected animals a two day inactivation in 4% formaldehyde was actually needed for stopping the mycelial growth. After this intense inactivation, no fungus growth was observed either in liquid medium (MEB) or on agar plates (YM).…”

“…The ions identified by REIMS can consequently be probed in biological tissue material. However, single MSI is often not sufficient and more imaging tools have to be used in concert to solve specific biological questions (Pluhacek et al, 2016).…”

Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights

“…By looking at metal species, researchers have the unique advantages of low background noise along with good quantitative dynamic range, unlike most protein or peptide studies. 225 Unfortunately, only select ionization sources are capable of imaging metals, and each method is limited in which metals they can image. 226 Currently, laser ablation-inductively coupled plasma (LA-ICP) MS 32,225,227–230 and SIMS 24,231 have been the only methods available to analyze elemental metals.…”