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Brain magnetic resonance imaging and computed
tomography ndings in cats and dogs with central
nervous system cryptococcosis in Australia:
23 cases (2009–2020)
Else Jacobson, BVSc1*; Juan Podadera, Med Vet2; Jia Wen Siow, DVM2,3; Dennis J. Woerde, BVSc4,5;
Mary F. Thompson, PhD6,7; Anna Tebb, MVM8; Zoe della Valle, BVSc9; David Collins, BVSc10; Richard Malik, PhD11
1Department of Internal Medicine, Veterinary Specialist Services, Underwood, QLD, Australia
2Department of Radiology, University Veterinary Teaching Hospital Sydney, School of Veterinary Science, University of Sydney,
Camperdown, NSW, Australia
3Department of Radiology, Small Animal Specialist Hospital, North Ryde, NSW, Australia
4Department of Internal Medicine, Animal Referral Hospital, Homebush West, NSW, Australia
5William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA
6Department of Internal Medicine, The Animal Hospital, School of Veterinary Medicine, Murdoch University, Murdoch, WA, Australia
7Department of Internal Medicine, University Veterinary Teaching Hospital Sydney, School of Veterinary Science, University of
Sydney, Camperdown, NSW, Australia
8Department of Internal Medicine, Western Australian Veterinary Emergency and Specialty, Success, WA, Australia
9Department of Internal Medicine, Melbourne Veterinary Specialist Centre, Glen Waverley, VIC, Australia
10Department of Internal Medicine, Northside Veterinary Specialists, Terrey Hills, NSW, Australia
11Centre for Veterinary Education, Sydney School of Veterinary Science, University of Sydney, NSW, Australia
*Corresponding author: Dr. Jacobson (ejacobson@vss.net.au)
Cryptococcosis is a deep mycosis caused by mem-
bers of the Cryptococcus neoformans and Cryp-
tococcus gattii species complexes. These environ-
mental organisms cause primary or opportunistic
infections in people and animals, with the CNS and
OBJECTIVE
To describe the imaging ndings in Australian cats and dogs with CNS cryptococcosis.
ANIMALS
23 cases (10 cats; 13 dogs) with CNS cryptococcosis and brain MRI or CT studies available to review.
METHODS
Retrospective, multi-institutional case series. Brain MRI or CT studies were reviewed by a board-certied radiologist.
Imaging ndings were described and the dierences between cats and dogs explored.
RE S U LT S
Morphologic features were consistent with extra-axial lesions in all (n = 13) dogs and either intra-axial (5/10) or
extra-axial (4/10) lesions in cats, with 1 cat having no detectable lesions in low-eld brain MRI scans. Meningeal ab-
normalities were most common, followed by forebrain and cerebellar lesions. Intracranial MRI lesions were typically
T2 hyperintense and T1 hypo- to isointense. Four cases had T2 hypointense lesions aecting the brain, sinonasal
cavity, or regional lymph nodes. Intracranial CT lesions were mostly soft tissue attenuating. Contrast enhancement
was present in all cases with contrast series available, with ring enhancement shown only in cats. Osteolysis was
more common in dogs than cats, particularly aecting the cribriform plate. All 13 dogs and many (6/10) cats had
at least 1 lesion aecting sinonasal or contiguous tissues, and locoregional lymphadenomegaly was common (7/10
cats; 11/13 dogs).
CLINICAL RELEVANCE
Imaging lesions in cryptococcal meningoencephalitis were extra-axial in dogs but could be intra-axial or extra-axial
in cats. Careful examination for extracranial lesions (sinonasal, retrobulbar, facial soft tissue, tympanic bullae, or
locoregional lymph nodes) is important to provide alternative safe biopsy sites. T2 hypointense lesions, while rare,
should prompt consideration of cryptococcosis.
Keywords: cat, dog, CT, MRI, cryptococcosis
Received September 6, 2023
Accepted November 17, 2023
doi.org/10.2460/javma.23.08.0454
©AVMA
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eye frequently aected.1,2 The infective organisms
have dierent geographic distributions, likely due
to the availability of disparate environmental niches.
Basidiospores or desiccated yeast cells are typically
inhaled, ltered by the upper respiratory tract, or
deposited in the bronchi or alveoli. If the organisms
escape clearance, multiply and progress beyond
colonization, a primary respiratory infection ensues.
Cats and dogs typically develop rhinosinusitis,1,3,4
while people, horses, and alpacas develop lower re-
spiratory tract disease, with either tracheobronchial
lesions or mycotic pneumonia.2,4 Dissemination to
the CNS is frequent, and in humans it occurs hema-
togenously, typically after an asymptomatic pulmo-
nary infection and a variable latent period in the hilar
lymph nodes.2 In contrast, CNS involvement in cats
and dogs is thought to often occur via direct exten-
sion of sinonasal lesions through the neurocranium,
as evidenced by the frequent co-occurrence of upper
respiratory tract and neurologic signs1,3–5 and limited
imaging ndings.6,7
Cross-sectional imaging studies of the head are
vital to inform our understanding of disease patho-
genesis in feline and canine CNS cryptococcosis.
They also allow optimization of therapy to improve
outcomes for these patients, which have a guarded
prognosis.5,6,8,9 Only limited reports of MRI or CT
ndings in cats and dogs with CNS cryptococcosis
exist. Sykes6 described the MRI or CT ndings in
cats (n = 6) and dogs (9) from northern California
with CNS cryptococcosis, while other reports docu-
ment only 1 or 2 cases of CNS involvement in cats or
dogs.7,10–15 In the California study,6 MRI of the brain
commonly showed multifocal or solitary parenchy-
mal lesions that were hyperintense on T2-weighted
(T2W) images, hypointense on T1-weighted (T1W)
images, and variably contrast enhancing. These au-
thors6 suggested that cats with CNS infection tend
to develop lesions consistent with gelatinous pseu-
docysts (T2 hyperintense but with more T1 intensity
than expected for acellular uid and only peripheral
contrast enhancement), while dogs develop cryp-
tococcal granulomas (more consistently contrast
enhancing, with a marked inammatory response in
histopathological sections).
In people with CNS cryptococcosis, MRI and CT
abnormalities commonly manifest as meningeal en-
hancement, dilated perivascular (Virchow-Robin)
spaces, pseudocysts (also called gelatinous pseu-
docysts or “soap bubbles”), and masses or nodules
diagnosed presumptively or histopathologically as
cryptococcal granulomas (“cryptococcomas”),16–18
with secondary hydrocephalus and infarction also
frequently reported.18,19 Dilated Virchow-Robin
spaces and pseudocysts are typically hypo- to isoin-
tense on T1W imaging and hyperintense on T2W and
FLAIR sequences, with no restricted diusion and
no contrast enhancement. Lesions < 3 mm in diam-
eter are classied as dilated Virchow-Robin spaces,
while those > 3 mm are called pseudocysts. They
typically occur in the basal ganglia and surround-
ing regions.18,20,21 Cryptococcomas are T1 hypo- to
isointense and T2 hyperintense masses or nodules
that are distributed more widely through the brain
parenchyma; they may exhibit mass eect and vari-
able patterns of contrast enhancement.18,21
It has been proposed that host immune sta-
tus may inuence the type of cryptococcal lesions
observed, with cryptococcomas more common in
immunocompetent hosts compared with immuno-
compromised people, where meningitis is typical.22
Despite this, it is likely that lesions exist on a spec-
trum, as both cryptococcomas and gelatinous pseu-
docysts are composed of a mix of organisms, mucoid
polysaccharide capsular material, and inammatory
cells, and in all cases there are pseudocystic areas on
gross and microscopic examination.17 One of the ma-
jor limitations when reviewing the available literature
is the lack of detailed descriptions of imaging lesions
or of denitions for the terms “pseudocyst” versus
“cryptococcoma,” with some studies using the terms
interchangeably. Findings in human studies with > 50
patients undergoing brain MRI or CT are tabulated
elsewhere (Supplementary Table S1).
This paper is the second in a series describing
the clinical presentation, imaging ndings, and out-
comes of Australian cats and dogs with CNS crypto-
coccosis.5 The objective of the present study was to
describe the brain MRI and CT ndings, compare and
contrast these ndings in cats versus dogs, and cor-
relate neuroradiologic abnormalities with imaging
abnormalities in the extracranial contiguous tissues,
particularly the sinonasal cavity.
Methods
Case selection
Referral centers in all Australian mainland states
were invited to participate. Databases from cooper-
ating veterinary referral centers were retrospectively
searched (without date restriction) for cats and dogs
diagnosed with cryptococcosis. Cases were included
if (i) the diagnosis was conrmed by mycologic cul-
ture, serology for cryptococcal antigen, or identica-
tion of characteristic organism morphology using cy-
tologic or histologic examination; (ii) they had CNS
abnormalities identied in the history, on neurologic
examination, on clinicopathologic testing, or in im-
aging studies; and (iii) brain MRI or CT studies (not
just reports) were available for review.
Diagnostic imaging acquisition
MRI sequences were obtained with either a
high-eld 1.5 Tesla (Intera, Koninklijke Philips NV;
Signa, GE Healthcare) or low-eld 0.2 Tesla (Vet-MR
Grande; Esaote) MRI system depending on the prac-
tice. All brain studies comprised T1W and T2W im-
ages in orthogonal planes. Additional FLAIR, STIR,
gradient echo, and diusion-weighted sequences
were obtained for some patients. T1W images were
also obtained after administration of an IV gadolini-
um-based contrast agent in all cases, except 1 dog.
CT images were obtained using various CT scan-
ners depending on the practice and the year in which
imaging was performed (SOMATOM Sensation 64,
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Scope, Emotion 16, or go.UP, Siemens; BrightSpeed
16 or LightSpeed QX/I, GE Healthcare). Contrast-
enhanced CT images were acquired after IV adminis-
tration of iohexol in all cases, except 1 dog.
Review of diagnostic imaging studies
DICOM images from all MRI and CT studies were
obtained and reviewed by a board-certied radiolo-
gist (JP) or resident-in-training (JWS) under the di-
rect supervision of a specialist radiologist. Reviewers
were aware of the diagnosis of cryptococcosis, but
images were reviewed without knowledge of case
details. Lesions were characterized by anatomic lo-
cation, signal intensity (for MRI studies), attenuation
(for CT studies), and contrast enhancement. Presence
of osteolysis, intracranial mass eect, brain hernia-
tion, and perilesional brain edema were also recorded.
Detailed analysis of contrast enhancement was not
performed as contrast administration and subsequent
image capture protocols were not standardized.
Terminology
Intracranial lesions were classied as extra-axial
if there was a mass arising outside the brain paren-
chyma or isolated meningeal or cranial nerve abnor-
malities. Lesions were classied as intra-axial if they
arose from within the brain parenchyma without af-
fecting the ventricular system other than via exter-
nal compression. Some cases with intra-axial lesions
also had meningeal enhancement. MRI intracranial
lesions were further classied as gelatinous pseu-
docysts if they were hyperintense on T2W images,
were hypo- to isointense on T1W images but with
more intensity than expected for acellular uid, and
had minimal or ring contrast enhancement. Lesions
were classied as cryptococcomas if they had low to
intermediate T1 intensity, had T2 hyperintensity, and
displayed more consistent contrast enhancement.
Statistical analysis
Data from review of diagnostic imaging studies
were tabulated and frequencies calculated (Excel;
Microsoft Corp). Two-tailed Fisher exact tests were
used to determine whether categorical variables
(anatomic location of imaging lesions and imaging
features; ie, intracranial mass eect, brain edema,
herniation, and osteolysis) diered in frequency be-
tween cats and dogs. Analyses were performed us-
ing SPSS Statistics (version 28; IBM).
Results
The initial database search identied 119 cases
(63 cats; 56 dogs) with a diagnosis of cryptococco-
sis. Fifty cases (19 cats; 31 dogs) were deemed to
have neurologic involvement and the clinical nd-
ings and outcomes for these have been published
previously.5 Of these, 23 cases (10 cats; 13 dogs)
had brain MRI or CT studies performed with image
sequences available for review. These 23 cases that
comprised the present study cohort were presented
to referral centers between 2009 and 2020 inclusive.
Imaging modality and region
Either MRI or CT was performed in each case. MRI
was performed in 11 of 23 cases (6/10 cats; 5/13
dogs) and CT was performed in 12 of 23 cases (4/10
cats; 8/13 dogs). The reason for the choice of mo-
dality was not stated in any of the medical records.
All MRI studies were of the brain, while the CT studies
included the whole head in all cases, except for in 1
cat that had only the brain imaged. All cases in which
the brain was the primary anatomic region imaged
had caudal upper respiratory tract structures visible,
with many of the MRI studies showing most of the up-
per respiratory tract in sagittal and dorsal planes. MRI
studies were high eld (1.5 Tesla) in 3 dogs and low
eld (0.2 Tesla) in 2 dogs and all cats (n = 6).
Reason for performing CT or MRI study
Imaging studies were performed as part of the
initial diagnostic work-up in all but 1 dog, in which
CT was performed to investigate sudden neurologic
deterioration following minor head trauma while on
long-term treatment for stable CNS cryptococcosis.
In other cases, imaging was performed to investigate
signs that localized to the brain (with or without up-
per respiratory signs; 6/10 cats; 4/11 dogs for which
the reason was known) or the upper respiratory tract
(2/10 cats; 3/11 dogs) or to determine the extent of
known cryptococcal disease (2/10 cats; 4/11 dogs).
Neuroanatomic imaging lesion location
In this section, we present the location and extent
of lesions within the CNS. Subsequent sections detail
the specic MRI and CT changes associated with CNS
lesions and describe any extracranial lesions identied.
Neuroimaging lesions consistent with crypto-
coccosis on MRI or CT were present in all cases, ex-
cept 1 cat that had a normal brain MRI study. The
meninges were most frequently aected, followed
by the forebrain, cerebellum, cranial nerves, cer-
ebellopontine angle, and brain stem (Table 1). The
cat with no detectable CNS lesion had only low-eld
brain MRI performed. It had presented with a his-
tory of collapse and had marked mandibular lymph-
adenomegaly on physical examination and MRI
studies. Cryptococcal meningitis was conrmed on
CSF analysis cytologically and via PCR, and crypto-
coccal organisms were identied cytologically and
mycologically (C neoformans var grubii) from the
aected lymph node.
CNS imaging lesions were extra-axial in all 13
dogs (5/5 MRI; 8/8 CT). In cats, lesions were extra-
axial in 4 cats (2/6 MRI; 2/4 CT) and intra-axial in
5 cats (3/6 MRI; 2/4 CT). Dogs showed extra-axial
lesions more frequently than cats (P = .002; Table
1). One dog with brain MRI performed had both
intra-axial (temporal lobe) and extra-axial (olfac-
tory bulb) mass lesions noted. Extra-axial lesions
involved only the meninges with or without cranial
nerves in 2 of 10 cats (1/2 MRI; 1/2 CT) and 7 of
13 dogs (2/7 MRI; 5/7 CT), with the rest having
extra-axial mass lesions with or without meningeal
enhancement. Intra-axial lesions were multifocal
in 3 cats and solitary in 2 cats. The number and
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distribution of intra-axial and extra-axial mass le-
sions are presented (Figure 1).
MRI intracranial lesion morphology
Of the 11 cases imaged with MRI, 4 of 6 cats and
3 of 5 dogs had intracranial lesions beyond isolated
meningeal or cranial nerve enhancement. Most le-
sions were hyperintense on T2W images (3/4 cats;
2/3 dogs), hypo- to isointense on T1W images (3/4
cats; 3/3 dogs), and hyperintense on FLAIR images
(3/3 cats; 1/2 dogs; with FLAIR sequences available;
Figures 2 and 3). Post-gadolinium T1W images were
available for 6 cats and 4 dogs. Contrast enhancement
of lesions was seen in all cases, except for the cat with
no detectable intracranial lesion. The contrast en-
hancement pattern was variable, ranging from none
(for some intra-axial lesions in 2 cats with multifocal
disease) to homogenous enhancement. Generally,
dogs had lesions with more homogenous contrast en-
hancement than cats. Lesions consistent with gelati-
nous pseudocysts were seen in 3 cats, while lesions
consistent with cryptococcomas occurred in 1 cat and
2 dogs.
In 4 cases (3 cats; 1 dog) lesions were partially
(3 cats) or predominantly (1 dog) T2 hypointense
(Figure 4). These lesions included an intra-axial mass
in the parietal lobe (1 cat), nasal cavity mass with intra-
cranial extension through the cribriform plate (1 dog),
nasal cavity mass without direct intracranial extension
(1 cat), and markedly enlarged mandibular lymph node
(1 cat) in which cryptococcal lymphadenitis was con-
rmed on cytologic evaluation. These T2 hypointense
lesions had variable T1 intensity (ranging from hypo-
to hyperintense), were FLAIR hypointense, and had
variable contrast enhancement (ranging from none to
homogenous enhancement).
CT intracranial lesion morphology
Of the 12 cases imaged with CT, 3 of 4 cats
and 3 of 8 dogs had intracranial lesions beyond
isolated meningeal or cranial nerve contrast en-
hancement. Most lesions were soft tissue attenu-
ating (20 to 55 HU) in precontrast series. One dog
had hyperattenuating lesions in precontrast series
(an extra-axial lesion measuring 74 HU and a nasal
lesion measuring 91 HU). Contrast enhancement
Cats all Cats MRI Cats CT Dogs all Dogs MRI Dogs CT
(n = 10) (n = 6) (n = 4) (n = 13) (n = 5) (n = 8)
Anatomic region No. No. No. No. No. No. P value
Intracranial lesion location
Any intracranial lesion 9 5 4 13 5 8 .435
Extra-axial 4 2 2 13 5 8 .002
Intra-axial 5 3 2 1 1 0 .052
Meninges 7 5 2 13 5 8 .068
Forebrain 6 3 3 5 2 3 .414
Cerebellum 2 2 0 0 0 0 .178
Cranial nerve 1 0 1 1 0 1 > .99
Cerebellopontine angle 1 1 0 0 0 0 .435
Brain stem 1 1 0 0 0 0 .435
Intracranial mass eect,
brain edema, herniation
Intracranial mass eect 7 4 3 7 2 5 .669
Brain edema 4 2 2 2 2 0 .341
Herniation 4 2 2 2 1 1 .341
Extracranial lesion location
Any extracranial lesion 6 3 3 13 5 8 .024
Sinonasal cavity 5 3 2 13 5 8 .007
Retrobulbar 0 0 0 5 1 4 .046
Cutaneous/subcutaneous 1 1 0 2 1 1 > .99
Tympanic bullae 2 0 2 1 0 1 .560
Osteolysis
Osteolysis (total) 3 1 2 10 3 7 .040
Cribriform plate 1 1 0 9 2 7 .010
Sinonasal bones 1 0 1 7 2 5 .074
Sphenoidal bones 2 0 2 3 0 3 > .99
Other neurocranium 0 0 0 4 1 3 .104
Lymphadenomegaly
Lymphadenomegaly (all) 7 5 2 11 4 7 .618
Retropharyngeal 6 4 2 7 2 5 > .99
Mandibular 1 1 0 9 3 6 .010
Supercial cervical 0 0 0 1 0 1 > .99
Deep cervical 0 0 0 1 0 1 > .99
Table 1—Anatomic locations and characteristics of lesions identied on MRI or CT in 10 cats and 13 dogs with CNS
cryptococcosis. Abnormalities are listed in decreasing order of frequency. P values are shown for Fisher exact tests
where the null hypothesis is that the frequency is the same in cats (all) and dogs (all).
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5
of meninges or other CNS lesions occurred in all
cases with contrast series available to review (4
cats; 7 dogs). Three cats had peripherally enhanc-
ing intracranial lesions (intra-axial in 2 cats and
extra-axial in 1 cat; Figure 5).
Intracranial mass eect and brain edema
and herniation
Intracranial mass eect was noted in over half of the
cases (7/10 cats; 7/13 dogs), while brain edema was not-
ed in around a quarter of the cases (4/10 cats; 2/13 dogs).
Brain herniation occurred in 6 of 23 patients: 4 of 10 cats
and 2 of 13 dogs (transtentorial only in 1 dog and 1 cat, and
both transtentorial and through the foramen magnum in 1
cat on MRI images; transtentorial in 2 cats and through the
foramen magnum in 1 dog on CT images).
Osseous lesions
Osteolysis was a common nding (3/10 cats; 10/13
dogs). The cribriform plate was most frequently aect-
ed, followed by the sinonasal bones, sphenoidal bones,
and other neurocranial bones. Osteolysis was seen more
frequently in dogs than cats, both overall (P = .040) and
aecting the cribriform plate specically (P = .010; Table
1). Hyperostosis was noted in 2 dogs on CT, 1 of which
also had osteolysis.
Extracranial imaging lesions
All dogs (13/13) and 6 of 10 cats had at least 1 im-
aging lesion outside the CNS (Table 1). Lesions involved
the sinonasal cavity (5/10 cats; 13/13 dogs), retrobul-
bar structures (0/10 cats; 5/13 dogs), facial cutane-
ous or subcutaneous tissues (1/10 cats; 2/13 dogs),
or tympanic bullae (2/10 cats; 1/13 dogs). Dogs more
frequently showed overt sinonasal cavity lesions than
cats (P = .007). Of the cases with extracranial lesions,
all dogs (13/13) and 2 of 6 cats were considered to
have direct intracranial extension of cryptococcal dis-
ease. Animals were considered to have direct disease
extension if they had sinonasal lesions with adjacent
osteolysis of the neurocranium or adjacent sinonasal
and extra-axial lesions that bridged the neurocranium.
Lymphadenomegaly
Regional lymphadenomegaly was noted in most
cases (7/10 cats; 11/13 dogs), with multiple lymph
Figure 1—Neuroanatomic locations of extra-axial and intra-axial mass lesions identied on MRI and CT images in 10
cats and 13 dogs with CNS cryptococcosis shown schematically on a normal midline sagittal T2-weighted (T2W) MRI
image. Locations of (A) extra-axial lesions in cats, (B) intra-axial lesions in cats, (C) extra-axial lesions in dogs, and (D)
intra-axial lesions in dogs are shown. The number of animals aected in each region is depicted by the number in the
center of the circle, with larger circles denoting multiple lesions aecting a particular site. Extra-axial regions aected
by mass lesions were the olfactory bulbs (1 cat; 5 dogs), the frontal lobe (1 dog), and adjacent to the sphenoid bones
(1 cat). Intra-axial regions aected were the parietal lobe (3 cats), temporal lobe (1 cat; 1 dog), occipital lobe (1 cat),
cerebellum (2 cats), cerebellopontine angle (1 cat), and pons (1 cat). Some animals had more than 1 lesion (3 cats had
multifocal intra-axial lesions, and 1 dog had both an intra-axial and extra-axial lesion). Background images were used
with permission from the University of Minnesota Canine Brain MRI Atlas (dog) or Gray-Edwards et al50 (cat).
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6
nodes aected in 1 cat and 5 dogs. Retropharyngeal
lymph nodes were most frequently aected, followed
by mandibular, supercial cervical, and deep cervical.
Dogs more frequently had mandibular lymphadeno-
megaly than cats (P = .010; Table 1). Palpable lymph-
adenomegaly was noted in the medical record in 3 of
7 cats and 4 of 11 dogs with abnormal lymph nodes in
imaging studies. Cryptococcal organisms were identi-
ed cytologically or mycologically from all head and
neck lymph nodes sampled (1 cat; 2 dogs).
Detection of cryptococcal organisms from
anatomic locations with imaging lesions
Cryptococcal organisms were identied by cyto-
logic, histologic, culture, or molecular means from 1
or more sites with an imaging lesion in the majority
of cases (6/10 cats; 12/13 dogs). Sites of organism
identication were CSF (5/10 cats; 4/13 dogs), si-
nonasal cavity (1/10 cats; 7/13 dogs), lymph nodes
(1/10 cats; 2/13 dogs), or facial swelling (0 cats; 1/13
dogs). Cryptococcal species isolated were C neofor-
mans (2 cats; 6 dogs; further characterized as C neo-
formans var grubii in 1 cat), C gattii (1 dog), and Cryp-
tococcus species not further identied (1 dog).
Clinically silent lesions detected by imaging
Clinically silent imaging lesions were detected in
over half of the cases. CNS imaging lesions without re-
ferable neurologic signs were noted in 2 of 10 cats and 4
of 13 dogs, although in 2 of these cats and 1 dog, non-
specic signs such as lethargy and hyporexia were noted,
which may reect intracranial involvement. Sinonasal
imaging lesions without any corresponding respiratory
signs were present in 2 of 10 cats and 6 of 13 dogs.
Figure 2—MRI transverse slices showing a parietal lobe lesion in a 1-year-old neutered male Ragdoll cat with mul-
tifocal intra-axial cryptococcomas. Corresponding low-eld MRI images in axial planes are shown for (A) T2W, (B)
T1-weighted (T1W) precontrast, (C) FLAIR, and (D) T1W post-gadolinium contrast sequences. The mass lesion (ar-
rowheads) is T2 hyperintense, T1 hypo- to isointense, FLAIR hyperintense, and contrast enhancing.
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7
Figure 3—MRI transverse slices showing an intra-axial temporal lobe lesion in a 2-year-old spayed female Border
Collie dog with multifocal intracranial cryptococcomas. This dog also had nasal cavity disease, cribriform plate lysis,
and an extra-axial lesion in the region of the left olfactory bulb (images not shown). Corresponding low-eld MRI im-
ages in axial planes are shown for (A) T2W, (B) T1W precontrast, (C) FLAIR, and (D) T1W post-gadolinium contrast
sequences. The lesion (arrowheads) is T2 hyperintense, T1 isointense, FLAIR hyperintense, and contrast enhancing.
Figure 4—T2W MRI sagittal image of a T2 hypointense
mass lesion in a 1.5-year-old intact female Labrador Re-
triever dog. The mass lesion (arrowheads) in the ethmo-
turbinate region extends through the cribriform plate into
the olfactory bulbs of the cerebrum. Surrounding cerebral
edema and frontal sinusitis are also present. Cryptococcal
isolate: Cryptococcus neoformans. T2W high-eld MRI im-
age, median sagittal plane.
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8
Discussion
To the best of our knowledge, this was the largest
series of cats and dogs with CNS cryptococcosis sub-
jected to cross-sectional imaging. Previous studies have
included only 1 or 2 cases,7,10–14 with a single larger se-
ries including 6 cats and 9 dogs with CNS cryptococco-
sis.6 This excellent case series from the University of Cal-
ifornia-Davis was noteworthy as northern California has
great diversity among C gattii isolates, and so unusual
and severe lesions may in part be attributed to dierenc-
es in virulence impacting pathogenesis. Median survival
times were shorter in the Californian series than recently
reported Australian data (13 days vs 1,556 days in cats,
and 7 days vs 638 days in dogs), although care needs
to be taken with direct comparisons. Other reasons for
variation in clinical and imaging ndings in patients with
cryptococcosis may include the following: (i) when the
case is presented for veterinary investigation (early vs
late in the disease course); (ii) treatments administered
by the referring veterinarian, especially corticosteroids;
and (iii) host species (ie, cat vs dog vs ferret).
Cats and dogs were relatively evenly proportioned
in the present study. Previous case series of feline and
Figure 5—Representative CT lesions in 2 cats and 2 dogs with CNS cryptococcosis. A—A 14-year-old spayed female
domestic shorthair cat with a nasopharyngeal mass and sphenoidal bone lysis with overlying extra-axial broad-based
peripherally contrast-enhancing mass (arrowheads). B—A 7-year-old spayed female domestic shorthair cat with multifo-
cal, intra-axial, ring-enhancing lesions with mass eect (arrowheads). C—A 4-year-old spayed female Dalmatian dog with
abnormal tissue in the nasal cavity extending into the frontal sinus and through areas of osteolysis in the frontal bone
(white arrowheads) into the subcutaneous tissues, and through the cribriform plate (black arrowhead). Cryptococcal
isolate: Cryptococcus gattii molecular type VGI. D—A 2-year-old entire female Doberman dog with abnormal soft tissue
occupying most of the right nasal cavity. There is leftward displacement of the nasal septum with areas of lysis (white ar-
rowhead) and extension of the abnormal tissue into the left nasal cavity. There is cribriform plate lysis (black arrowhead)
with extension of abnormal material into the right olfactory bulb region. All images are contrast enhanced, soft tissue
window (window level, 40 HU; window width, 300 HU), in sagittal (A and C) or axial (B and D) planes.
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9
canine cryptococcosis in Australia and the US have
shown cats to be up to 8 times more likely to develop
cryptococcosis than dogs.1,3,4 Dogs, however, have a
propensity for early dissemination and more common-
ly have CNS involvement than cats.1,3,4 This provides
greater justication for MRI or CT imaging in this spe-
cies, which creates considerable selection bias toward
canine cases in our study. This is supported by similar
numbers of cats and dogs being involved when only
cases with intracranial cryptococcosis were reviewed.5,6
Extra-axial CNS disease predominated in dogs, while
in cats there was a relatively even distribution of intra-axi-
al and extra-axial lesions. In dogs, extra-axial lesions were
focused on the cribriform plate, and in all cases, direct
extension of disease from sinonasal lesions was consid-
ered the likely portal of intracranial entry. In contrast, only
2 cats were considered to have direct disease extension
from the upper respiratory tract, and in 1 of these it was
via the sphenoidal sinus. Feline intra-axial lesions were
clustered around the caudal cortical regions (parietal,
temporal, and occipital lobes), brain stem, and cerebel-
lum, which may suggest that hematogenous dissemina-
tion is more common in this species. In support, a cat with
neurologic signs in Taiwan that underwent head CT and
postmortem examination had multifocal cryptococcomas
in the region of the basal ganglia with cryptococcal or-
ganisms in the Virchow-Robin (perivascular) spaces but
without detectable sinonasal abnormalities.15 In people,
cryptococcal meningitis typically results from hematog-
enous dissemination from intrathoracic lesions and, very
rarely, from abdominal structures such as the intestines.2
The thorax was not routinely imaged in the present study
to evaluate this possibility, although pulmonary crypto-
coccosis is reported infrequently in cats and dogs.23,24 It
is likely that species-specic behaviors and dierences in
respiratory physiology related to airow result in initial in-
oculation and colonization of the sinonasal cavity, rather
than the bronchial tree or lungs of cats and dogs. In cats,
therefore, hematogenous dissemination probably occurs
from sinonasal rather than pulmonary lesions. Rapid dis-
semination to the brain has been shown in mouse models
following intranasal inoculation,25 although an earlier ex-
perimental model in cats failed to demonstrate dissemi-
nation following intranasal inoculation.26
Some interesting and unprecedented imaging fea-
tures were noted in the present MRI and CT studies. Four
cases had lesions with hypointensity on T2W MRI im-
ages. T2 hypointense intracranial lesions are uncommon
but can occur with paramagnetic components (contrast
media, blood, mineral, or melanin), lack of excited pro-
tons (air-containing spaces or turbulent and rapid ow
of blood or CSF), high viscosity in mucus- or protein-
containing lesions, and highly cellular lesions with de-
creased extracellular uid.27 To the authors’ knowledge,
such lesions have not previously been reported in feline
or canine cryptococcosis and have been rarely reported
in people with histopathologically conrmed cryptococ-
comas.28,29 T2 hypointense lesions have, however, been
identied in 2 dogs with noncryptococcal fungal brain
granulomas in the US..30 In the present study, T1 sig-
nal was variable but tended to be hypo- to isointense
in most of the T2 hypointense lesions. Possible expla-
nations for T2 hypointense lesions in feline and canine
cryptococcosis include fungal production of melanin as a
virulence factor (although this would typically be T1 hy-
perintense)31; accumulation of mineral substances such
as calcium, which has been identied histologically in a
person with hepatic and pulmonary cryptococcomas29;
high mucin or protein composition of cryptococcal le-
sions due to the accumulation of capsular material; or
hypercellular lesions such as cryptococcomas. Another
feature noted on CT was ring contrast enhancement of
lesions in cats. Ring enhancement has been reported in
HIV-negative (but not necessarily immune-competent)
people32 and cats6 with CNS cryptococcosis. It is possi-
ble that these lesions represent gelatinous pseudocysts,
although previous reports of such lesions in cats6 and
humans21,32–36 were based on MRI examination.
MRI lesions consistent with gelatinous pseudocysts
were identied in 3 cats in the present study. It has
been postulated that the development of pseudocysts
may be related to the immune status of the patient. In
human studies, gelatinous pseudocysts are most fre-
quently seen in patients with HIV infection or other un-
derlying disease. Furthermore, pseudocysts have been
most frequently identied in HIV-positive patients not
undergoing anti-retroviral therapy.20,35 Of the 5 cats
receiving corticosteroids prior to diagnosis of crypto-
coccosis in our study, 1 developed lesions consistent
with pseudocysts on MRI images and 2 developed ring-
enhancing intra-axial lesions on CT images.
Brain herniation was noted more frequently in cats
(4/10) than dogs (2/13) in the present study, although
this dierence was not statistically signicant. In the
wider cohort of cats with CNS cryptococcosis from
which this imaging study was derived, CSF collection
was associated with decreased survival.5 The poorer
outcome in cases undergoing CSF collection may be
due to brain herniation from raised intracranial pressure
or space-occupying lesions. Therefore, where possible,
brain imaging should ideally be performed prior to CSF
collection to mitigate the risk of adverse outcomes.
Other than cryptococcosis, aspergillosis is a com-
mon mycosis of cats and dogs worldwide with a pro-
pensity to aect the sinonasal cavity and contiguous
tissues. Sinonasal aspergillosis is most commonly
caused by Aspergillus fumigatus. Sino-orbital asper-
gillosis is a distinct form of fungal rhinosinusitis rec-
ognized in cats, commonly caused by Aspergillus felis.
CT imaging ndings have been reported for feline sino-
orbital and feline and canine sinonasal aspergillosis.37,38
Sinonasal aspergillosis diers from cryptococcosis in
that it tends to be conned to the upper respiratory
tract (with turbinate lysis a dening feature), and while
orbital bone and cribriform plate lyses occur,37,38 it is
generally considered noninvasive. Feline sino-orbital
aspergillosis and feline and canine cryptococcosis have
commonalities, namely their tendency to form granu-
lomas and invade locoregional tissues (including the
CNS) following sinonasal cavity infection.38 CT imaging
of mass lesions in cats with both diseases (sino-orbital
aspergillosis and cryptococcosis) shows rim enhance-
ment.6,38 Interestingly, in the present study, no cats had
retrobulbar involvement, which may provide a key dis-
tinguishing feature between cryptococcosis and sino-
orbital aspergillosis in cats.
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10
One of the biggest challenges imaging human cryp-
tococcal meningitis is the propensity for lesions to be
misdiagnosed as neoplastic,39 and the same is probably
true in relation to CNS disease in companion animals.30
The diculty in dierentiating inammatory, neoplastic,
and vascular causes of imaging lesions, particularly in the
brain in cats and dogs, is well-known.40–42 Improved un-
derstanding of the MRI and CT morphologic features of
cryptococcal lesions may enable us to create an index of
suspicion for this disease to ensure its appropriate inclu-
sion in the dierential diagnosis and tailor investigations
accordingly. Aspects that might alert the clinical team to
a cryptococcal lesion include extracranial abnormalities
on whole-head imaging (eg sinonasal or retrobulbar),
as clinically silent lesions are common in cryptococco-
sis, and enlargement or contrast enhancement of lo-
coregional lymph nodes. Such lesions may also provide
readily accessible, low-risk biopsy sites. Furthermore,
the choice of imaging modality might be germane; for
example, brain MRI is more sensitive in detecting crypto-
coccal lesions in people than CT,17,43 although CT may be
more appropriate to detect osteolysis or allow rapid full-
head imaging when anesthetic stability is a concern. In
addition, CT is usually less expensive than MRI and takes
less time. Finally, optimization of contrast administration
and image capture protocols can improve the detection
of meningitis,44 while the use of techniques such as dif-
fusion weighted imaging, perfusion weighted imaging,
and CSF enhancement on postcontrast FLAIR sequenc-
es may be useful on the basis of human studies.35,45,46
Further research to investigate the utility of these tech-
niques in cats and dogs with cryptococcosis is needed.
Additional tools such as functional MRI imaging includ-
ing spectroscopy and nuclear medicine including posi-
tive emission tomography/CT or single photon emission
CT/CT may provide future avenues for imaging-based
diagnosis of cryptococcosis,47,48 although their availabil-
ity in veterinary medicine is currently limited.
A noteworthy aspect of the present study is the
presence of cryptic (ie, clinically silent) lesions detect-
ed with advanced imaging, namely intracranial and si-
nonasal lesions. Lesions in the sinonasal cavity provide
information about disease pathogenesis and enable
safer and less invasive sampling than CSF collection or
brain biopsy. Cryptococcal CNS involvement is associ-
ated with poorer outcomes. Detection of asymptomatic
CNS lesions may reect early detection using advanced
imaging, which therefore has the potential to improve
outcomes with the institution of earlier and more ag-
gressive therapy (amphotericin B in both cats and dogs
and ucytosine in cats only).8,9 Cryptic lesions are also
important when categorizing disease on the basis of an-
atomic distribution and making comparisons with pre-
vious studies, which often used only clinical criteria to
classify cases.3,4 Given the frequency of clinically silent
lesions in the present study, earlier reports may have
underestimated the extent of body system involvement
and attempts to compare ndings between studies that
use dierent methodology may be inappropriate. It is
possible that some lesions in the present study may rep-
resent concurrent noncryptococcal disease, as no intra-
cranial lesions were directly sampled and serial imaging
was not performed to assess response to treatment. In
addition, the retrospective nature of data recruitment
may have resulted in underreporting of clinical signs.
One cat in this series had conrmed cryptococcal
meningitis, but no imaging lesions could be identied
on brain MRI. Possible limitations that may explain this
include the use of low-eld MRI and nonstandardized
contrast administration and image capture protocols. In
human studies, both MRI and CT have failed to detect or
underestimated the extent of CNS cryptococcal infection
compared to autopsy ndings.16,17 Furthermore, in dogs,
1.5T MRI showed low sensitivity to detect histopathologi-
cally conrmed meningeal pathology.49 This highlights
the importance of pursuing further diagnostics such as
antigen serology in the rst instance and CSF collection
and analysis, even if there are no ndings on imaging.
Limitations of the present study related largely to its
retrospective design. Imaging modality varied between
cases, and although choice of MRI or CT was not explic-
itly stated in medical records, it was likely due to clinician
or imager preference, cost, or what was available locally
at the time of case presentation. Varied MRI and CT study
protocols were employed, and contrast administration
and subsequent image capture was not standardized.
Also, several brain MRI studies were performed using
low-eld MRI, which is inferior to high-eld scanners. In
addition, the present study was underpowered for some
of the statistically signicant dierences identied in the
frequency of imaging abnormalities between cats and
dogs. A post hoc sample size calculation was performed
and revealed that 44 cases would have been required to
achieve a power of 0.8 with a condence level of 0.95 for
all signicant ndings (https://epitools.ausvet.com.au/
twoproportions).
To our knowledge, this is the largest series of MRI
and CT ndings in feline and canine CNS cryptococcosis
reported. This study describes head MRI and CT nd-
ings in cats and dogs diagnosed with cryptococcosis.
Cryptococcosis should be included in the dierential
diagnosis for both intra-axial and extra-axial lesions,
and the nding of lesions in surrounding tissues and
lymph nodes should increase the index of suspicion for
an infection. Of note, some lesions are clinically silent.
Acknowledgments
The authors would like to thank Jennifer von Luckner and
Wen-Jie Yang for th e initial records sea rch at Murdoch University.
Disclosures
The authors have nothing to disclose. No AI-assisted
technologies were used in the generation of this manuscript.
Funding
The authors have nothing to disclose.
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