Round left lower lobe mass with surrounding “halo” of ground-glass attenuation.

The CT “halo sign” was first described in 1985 as an early sign of invasive pulmonary aspergillosis. This finding was seen to precede cavitation and the “air crescent sign” by 2-3 weeks. Cavitation is usually seen after the patient’s immune function recovers.

The ground-glass halo corresponds to hemorrhagic infarction of the surrounding lung tissue.

Kuhlman JE, Fishman EK, Siegelman SS. Radiology 1985;157:611-614.

This finding has subsequently been described in many other conditions:

• Infectious
  – Fungal (Aspergillus, Mucor, Candida, Coccidiomycosis…)
  – Mycobacterial (TB, MAI)
  – Bacterial (Nocardia, Legionella, Coxiella, Rickettsia)
  – Viral (CMV, HSV…)
• Neoplastic
  – Primary tumors (Bronchioalveolar Carcinoma, Squamous Cell Carcinoma, Kaposi sarcoma…)
  – Metastases (Angiosarcoma, melanoma, choriocarcinoma, osteosarcoma, …)
• Inflammatory
  – GPA (Wegener’s granulomatosis)
  – Eosinophilic pneumonia (Loeffler’s Syndrome)
  – Organizing pneumonia

Primack SL, Hartman TE, Lee KS, et al. Radiology 1994;190:513-515.
Kim Y, Lee KS, Jung KJ, et al. J Comput Assist Tomogr 1999;23:622-626.
Lee YR, Choi YW, Lee KJ, et al. Br J Rad 2005;78:862-865.
Webb WR, Brant WE, Major NM, eds. Fundamentals of Body CT. Philadelphia: Elsevier; 2006.

The CT halo sign in a febile immunosuppressed patient can be narrowed to infectious causes:

• Fungal (Aspergillus, Mucor)
• Mycobacteria (TB, MAI)
• Bacterial (Nocardia, Legionella)
• Viral (CMV)

Even more specific, here is the most common timing of infections after solid organ transplant:
< 1 month – nosocomomial bacterial infection (gram negative, S. aureus)
2-6 months – viruses (e.g. CMV), Fungi (Aspergillus, PCP), Opportunistic Bacteria (Nocardia)
>6 months – opportunistic infections are uncommon unless GVHD present (community acquired pneumonia e.g. Strep pneumoniae)

McLoud TC, Boiselle PM, eds. Thoracic Radiology: the Requisites. Philadelphia: Mosby; 2010.

Viruses resulting in the halo sign generally cause multiple small nodules. In this patient 3 months after transplant, we can say this is most likely an infection due to fungi or opportunistic bacteria.

This patient was diagnosed with Nocardia pneumonia.

It is important to remember that 18-F fluorodeoxyglucose (or FDG) is a nonspecific tracer depicting glycolysis in the body. Other processes such as infection may also be associated with increased glycolysis, for example due to influx of neutrophils and  other inflammatory cells.

This 60 year old woman intially presented with a nonproductive cough and later underwent an FDG PET/CT for evaluation of pulmonary mass:

After inconclusive biopsy, this lesion was resected and also found to represent Nocardia pneumonia. The patient was subsequently diagnosed with an atypical immunodeficiency syndrome.

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The search for useful infection-specific radiotracers is ongoing. Multiple single-photon emitting radiotracers more specific for infection have been used:

• Tc99m-labeled white blood cells – limited use in pumlmonary infection due to nonspecific lung uptake
• Tc99m fanlesomab (Neutrospect) – IgM antibody to CD15 (neutrophils), no longer available
• Tc99m sulesomab (LeukoScan) – IgG1 antibody Fab’ fragment, available in Europe for musculoskeletal infections
• Tc99m ciprofloxacin – radiolabeled antibiotic which has been used to detect active pulmonary TB

Ziessman HA, O’Malley JP, Thrall JH, eds. Nuclear Medicine, the Requisites, 4th ed. Philadelphia: Elsevier, 2014.
Lee M, et al. Tc-99m ciprofloxacin SPECT of pulmonary tuberculosis. Nucl Med Mol Imaging 2010;44:116-122.

PET tracers have also been evaluated for diagnosis of pulmonary infection (Cho S, et al. 124I-FIAU thymidine kinase-based PET imaging of lung infection. J Nucl Med 2013;54(supplement 2):649.), although although no infection-specific PET tracers are currently clinically available in the United States.