1. Nothing to Sniff At: A Radiologic Review of Olfaction
eEdE-146
Nothing to Sniff At: A Radiologic Review of Olfaction
Justin Brucker, MD
University of Rochester, NY

2. INTRODUCTION
Our sense of smell (olfaction) is arguably one of our oldest, most complex, and most important primary senses. However, it is often overlooked in the clinical setting.
The ability to detect aerosolized odorants probably evolved as a way for our primordial ancestors to assess the chemical environment around them, in order to avoid danger, obtain nourishment, and identify reproductive mates.
In modern humans, olfaction has the added importance of adding a dimension of pleasure to environmental interactions, such as with eating. Consequently, diseases that result in the loss of olfaction can significantly diminish an individual’s quality of life.
Furthermore, several CNS disorders can be heralded by a loss of olfaction – for example, as a prodrome to early neurodegenerative disease – and a failure to recognize these symptoms may adversely affect clinical outcomes.

3. PURPOSE This exhibit is intended to provide the viewer with:
An appreciation for the clinical significance of olfactory complaints
A framework to understand the mechanisms of odorant detection and perception
Exposure to a broad range a medical disorders that can be associated with olfactory disturbances
An appreciation for different imaging strategies used in obtaining radiologic evidence of olfactory disorders

4. Approaching Olfactory Disorders
It can be challenging to obtain objective evidence of olfactory disorders. It is helpful to define the type of complaint a patient has before ordering clinical and radiologic testing. For example, anosmia and hyposmia may be caused by a wide range of conductive, sensorineural , and central neural disorders – however, a history of hyperosmia, dysosmia, or phantosmia is a clue of a cortical processing abnormality.
In the clinical setting, olfaction testing may be as simple as determining the distance from the nose that a patient can detect an alcohol swab, or blinded comparison of prepared odorants versus control blanks. Various olfactory testing kits exist (“sniffin sticks” and scratch-n-sniff booklets), which can help analyze an olfactory complaint over a range of various odorants.
Physiologic testing, such as olfactory evoked potentials (electrographic analysis of parietal activity during olfactory stimulation) may help determine if there is an appropriate CNS response to smell. OEPs can be compared against other forms of endogenous brainwave activity (“contingent negative variation”) to see if the osmic complaint is peripheral or intrinsic to the CNS.
Type of Smell Distortion
Definition
Anosmia
Absent sense of smell
Hyposmia
Decreased detection of odor
Hyperosmia
Increased sensitivity to odor
Dysosmia
Distorted perception of smells
Parosmia/Phantosmia
Perception of smell without stimulus
Presbyosmia
Age-related decline in smell sensation

5. How do we smell? Step 1: Conduction
cribriform
plate
Conductive olfactory deficits are related to impaired transit of odorant molecules from the environment to the olfactory receptors – therefore, most of these issues usually arise from mechanical airflow problems in the sinonasal cavity, and result in either hyposmia or complete anosmia.
Successful conductive olfaction depends on several elements:
Airflow through the olfactory clefts
Humidification of inspired air
Absorption into normal mucus secretions
Presence of normal olfactory epithelium
olfactory
fossa
cribriform
plate
olfactory
cleft

6. How do we smell? Step 2: Detection
Converging olfactory neurons
Once an odorant molecule reaches the olfactory epithelium and dissolves through the overlying mucosal layer, it is able to interact with the olfactory receptors (sensorineural olfaction). These receptors are present on specialized sensory cilia that project from the apical pole of the bipolar cells (olfactory neurons). Bipolar cells form tight junctions with supporting sustentacular cells, both of which arise from the basal layer of the olfactory epithelium (pseudostratified columnar) and are replenished every couple weeks. Over time, the olfactory epithelium is replaced by normal respiratory epithelium, which may help explain why our sense of smell tends to diminish with age.
Several mechanisms for odorant-receptor activation have been proposed, including lock-and-key and molecular vibration detection models. Whatever the mechanism, activation of the G-protein olfactory receptor triggers initiation of a cAMP cascade and subesequent channel-mediated influx of cations (Na+ and Ca++), resulting in an action potential.
The chemical structure of odorant molecules appears to be an essential to their detection, although in humans there are only few hundred genes that encode for olfactory receptors. However, different olfactory receptors can be simultaneously activated by the various moieties present on a single molecule, thereby allowing for a combinatorial effect that markedly expands the repertoire for odorant discrimination. Furthermore, multiple bipolar cells converge their neuronal processes onto a single glomerulus within the olfactory bulb – thus providing another level of combinatorial processing of olfactory information, as well as a way to boost the signal to noise ratio of the stimuli. In the bulbs, reciprocal negative feedback from mitral and tufted cells onto the glomeruli may help further filter out true signal from background noise, or lead to adaptation of persistent olfactory stimuli.
To olfactory bulb
cribriform
plate
Lamina propria
basement membrance
bipolar cell
sustentacular cell = = = = =

7. How do we smell? Step 3: Perception
After sensorineural transduction of olfactory inputs from the olfactory neurons and bulbs, the information is transmitted back to the brain via different pathways:
olfactory trigone
Medial Olfactory Pathway:
This is the most primordial olfactory tract in the brain. Nerve impulses travel back along the medial olfactory striae , enter the anterior perforated substance and hypothalamus, and project to the limbic areas. It associates olfactory stimuli with autonomic and primitive behavioral responses.
Lateral Olfactory Pathway:
Impulses travel posterolaterally along the lateral olfactory striae and enter the medial temporal lobe, at the level of the amygdalya and peri-amygdaloid cortex (pyriform and pre-pyriform cortices), the hippocampus, and limbic system. It associates olfactory stimuli with memory and confers emotional valence.
Thalamocortical Pathway:
Olfactory inputs also project to the dorsomedial nuclei of the thalamus, with reciprocal connection to the orbitofrontal cortex. In concert with the other olfactory pathways, it is responsible for cognitive processing of olfactory stimuli.
lateral
olfactory
stria
olfactory sulcus
medial
olfactory
cortex
medial
olfactory
cortex
medial
olfactory
cortex
lateral
olfactory
cortex
(surrounding
amygdala)
lateral
olfactory
cortex
olfactory sulcus
rectus gyrus
olfactory
bulb
olfactory
bulb

8. Question #1: The detection of noxious olfactory stimuli is mediated through which sensorineural pathway?
Olfactory Nerve (CN II)
Trigeminal Nerve, Maxillary Division (CN V2)
Vomeronasal Organ
Kiesselbach’s Plexus
Vidian Nerve

9. Question #1: The detection of noxious olfactory stimuli is mediated through which sensorineural pathway?
Olfactory Nerve (CN II)
Trigeminal Nerve, Maxillary Division (CN V2)
Vomeronasal Organ
Kiesselbach’s Plexus
Vidian Nerve
 Correct Answer: B – In addition to providing somatosensory innervation to the sinonasal cavity (including sensitivity to touch, pain, and temperature), the maxillary division of the trigeminal nerve (CN V2) is also responsible for the detection of various chemical irritants and noxious chemosensory stimuli within the nasal cavity (e.g. ammonia, capsaicin, menthol, wasabi, smelling salts). This alternative route of olfactory detection is achieved via molecule-specific ion channel receptors present along the V2 nerve terminals, several of which belong to the transient receptor potential (TRP) family of ion channels. In the clinical setting, distinguishing the detection of normal odorants from chemical irritants may help characterize a patient’s olfactory complaint and identify cases of malingering.

10. Question #1: The detection of noxious olfactory stimuli is mediated through which sensorineural pathway?
Olfactory Nerve (CN II)
Trigeminal Nerve, Maxillary Division (CN V2)
Vomeronasal Organ
Kiesselbach’s Plexus
Vidian Nerve
Incorrect Answers:
A -- The olfactory nerves (CN II) are responsible for the detection of normal odorants.
C – The vomeronasal (Jacobson’s) organ is a remnant of the accessory olfactory system (CN II), inconstantly found in humans at the base of the anterior bony nasal septum, approximately. In non-humans, it plays an important role in pheromone detection and sex-steroid/hormone signaling; a homologous function has been proposed in humans, as well – perhaps providing a basis for the synchronization of menstrual cycles in female cohabitants, for example - although this is controversial. Embryologic projections from the VNO to the medial forebrain may serve as scaffolding for GnRH-secreting cells migrating to the hypothalamus, although these connections may not persist in fully developed humans.
D – Kiesselbach’s Plexus is a focal intervascular anastomosis comprised of the terminal branches of multiple arterial territories, located along the anterior-inferior nasal septum (Little’s area). It is often implicated in epistaxis, but it does not serve an olfactory function.
E – The vidian nerve is the combination of the sympathetic and parasympathetic nerves, arising from the deep petrosal nerve and greater superficial petrosal nerve, respectively. The vidian nerve provides efferent autonomic innervation to the sphenopalatine ganglion and sinonasal cavity. In contradistinction, afferent autonomic innervation to the sinonasal cavity is mediated by the vagus nerve (CN X).

11. ILLUSTRATIVE CASES

12. Congenital Arhinia A B C
Volume-rendered (A) , coronal (B), and sagittal (C) reconstructed CT images demonstrate complete bony atresia of the nasal cavity with associated non-formation of the nasal elements. This is associated with diminished size of the central midface and absence of the olfactory fossae (). In addition to an obvious conductive olfactory deficit – due to absence nasal air flow – this patient is also expected to have a sensorineural olfactory deficit; development of the olfactory epithelium and nasal cavity is very closely intertwined, with common origin from the olfactory placodes. Furthermore, there are common transcriptional pathways and patterning sequences that affect both olfactory tract and craniofacial formation.
Congenital absence of the nose and nasal cavity is a very rare entity, particularly in isolation from other anomalies (as with this patient, without identifiable chromosomal abnormalities). Craniofacial or other midline anomalies should always trigger a search for olfactory anomalies. In addition to issues with cosmesis, there can be associated abnormal interocular spacing with vision problems. Furthermore, these patients will require airway protection upon birth, since newborns are obligate nose breathers.

13. Craniofacial Dysmorphia (unspecified) with Associated Anosmia
Another example of congenital absence of the olfactory bulbs () in a patient with dysmorphic configuration of the craniofacial skeleton, with clinically observation of anosmia. However, the patient was otherwise neurologically and cognitively intact.
This case illustrates how the presence of craniofacial abnormalities should trigger surveillance for olfactory tract anomalies, and that such anomalies can also occur in isolation from a normal CNS.

14. Congenital Anosmia A
8-year-old female who was noticed to be unable to distinguish smells, otherwise with normal development.
Coronal (A) and axial (B) balanced steady-state images (FIESTA) demonstrate complete absence of the olfactory bulbs. The rectus gyri have prolapsed down into the otherwise empty olfactory fossae ().
Congenital absence of the olfactory bulbs is commonly thought of in association with Kallman Syndrome, which has the added feature of hypothalamic hypogonadism. However, Kallman syndrome is a very rare entity, and many instances of congenital anosmia (also rare) may be seen in isolation from other CNS problems. These cases can be either familial or sporadic. B

15. Bardet-Biedel SyndromeC
Coronal and axial T2 weighted imaging (A-B), there is asymmetric hypoplasia of the olfactory bulbs () that is worse on the left side, with the additional very subtle finding of a relatively diminutive left olfactory sulcus (). Additional imaging demonstrates echogenicity of the kidneys (C), as well as multiple skeletal abnormalities such as polydactyly (, D).
These are among the classic findings for Bardet-Biedl syndrome, a rare genetic condition associated hyposmia/anosmia, cognitive deficits, retinitis pigmentosum, and visceral/skeletal abnormalities. Olfactory deficits are secondary to failure to form the sensory cilia along the apical poles of the bipolar cells within the olfactory epithelium. D

16. Kartagener Syndrome A B C
Kartagener Syndrome is another example of a genetic ciliopathy, although unlike Bardet-Biedl syndrome, is characterized by the lack of normal kinocilia (moving cilia) instead of sensory cilia – this is due to the absence of the ATP-driven dynein arms that are normally present on the ciliary microtubules. The downstream consequences of this defect include impaired mucociliary clearance in the respiratory tract, infertility, and heterotaxy. Chronic sinonasal disease can result in a secondary conductive hyposmia due to obstruction of nasal air flow. A B C
Frontal sinus radiograph (A) demonstrates underpneumatization, sclerosis, and opacification of the frontal () and maxillary () sinuses, compatible with chronic sinusitis secondary to impaired mucociliary clearance.
Chest radiograph (B) and CT (C) illustrate situs inversus and varicose bronchiectasis.

17. Cystic Fibrosis A B
Mutation of Cl- transporter leads to increased viscosity of secretions
ENT manifestations of CF in % Pts (> 50% have nasal polyps)
Nasal polyposis, otitis media, acute and chronic sinusitis
Chronic sinusitis  endobronchial infections, airway reactivity, and duration of illness
Ddx: nasal polyposis, allergic sinusitis, Kartegener’s syndrome, aspirin-induced asthma and polyposis (Samter’s triad)
Sinonasal congestion resulting in conductive anosmia is commonly seen in many conditions. Chronic inflammatory maxillary sinusitis with hyperattenuating secretions (A-B) and bronchiectasis/fibrosis (C) in a child should raise suspicion for CF. Please note the normal position of the heart, helping us distinguish it from Kartagener Syndrome. C

18. Bardet-Biedl Syndrome (i.e. sensory ciliopathy)
Question #2: Which of the following conditions would be most expected result in a central sensorineural olfaction deficit?
Cystic Fibrosis
Kallman Syndrome
Bardet-Biedl Syndrome (i.e. sensory ciliopathy)
Congenital Insensitivity to Pain (CIP) Syndrome (i.e. voltage-gated Na+ channelopathy)
Kartagener Syndrome

19. Question #2: Which of the following conditions would be most expected result in a central sensorineural olfaction deficit?
Cystic Fibrosis
Kallman Syndrome
Bardet-Biedl Syndrome (i.e. sensory ciliopathy)
Congenital Insensitivity to Pain (CIP) Syndrome (i.e. voltage-gated Na+ channelopathy)
Kartagener Syndrome
Correct Answer: B –- Kallman Syndrome is a genetic syndrome that demonstrates a variable inheritance pattern, and is characterized by the clinical symptoms of hypogonadotropic hypogonadism and congenital anosmia/hyposmia. It represents the downstream consequence of impaired neurotaxis of cellular projections arising from the medial and lateral olfactory placodes into the telencephalic vesicles of the early developing forebrain, thereby interrupting migration of luteinizing hormone-releasing hormone (LHRH)-secreting cells to the hypothalamus and induction of the olfactory bulb, respectively. On imaging, the expected findings are absence or dysplasia of the olfactory bulbs, tracts, and sulci; this is consistent with a central sensorineural olfactory deficit.

20. Question #2: Which of the following conditions would be most expected result in a central sensorineural olfaction deficit?
Cystic Fibrosis
Kallman Syndrome
Bardet-Biedl Syndrome (i.e. sensory ciliopathy)
Congenital Insensitivity to Pain (CIP) Syndrome (i.e. voltage-gated Na+ channelopathy)
Kartagener Syndrome
Incorrect Answers:
A & E -- Cystic fibrosis (A) is a common inherited chloride channelopathy, characterized by abnormally viscous mucinous secretions and sinonasal polyposis in young people.
Kartagener Syndrome (E) is an inherited primary ciliary dyskinesia, characterized by impaired mucociliary clearance, bronchiectasis, diminished fertility, and heterotaxy.
Both of these conditions would be expected to result in a conductive hyposmia, due to sinonasal obstruction and abnormal mucus formation.
C & D – Bardet-Biedl Syndrome (C) is a rare genetic ciliopathy that is characterized by impaired olfaction, retinitis pigmentosum, hypogonadism, polydactyly, obesity, renal dysfunction, and cognitive impairment. In regards to olfaction, there is little to no formation of the specialized sensory cilia along the apical poles of the bipolar cells, thus resulting in a primary peripheral sensorineural olfactory deficit.
Congenital Insensitivity to Pain (CIP) Syndrome (D) is a rare voltage-gated sodium channelopathy that results in diminished synaptic signaling along the axonal

21. Sinonasal Polyposis and SinusitisB C D
Acute on chronic invasive sinusitis with hyposmia.
In addition to complete opacification and obstruction of the sinonasal cavity, there is erosion of the cribriform plates () on CT, with contiguous spread of enhancing inflammatory tissue through the anterior cranial fossa () on MRI. This would be expected to result in both conductive and sensorineural hyposmia, since there is obligate involvement of the olfactory bulbs. There is also dehiscence of the right lamina papyracea with subperiosteal abscess formation ().

22. Esthesioneuroblastoma (1/3)
Primary tumor of the olfactory epithelium
Also known as olfactory neuroblastoma
Bimodal age distribution, with largest incidence in young men (2nd decade of life) and secondary peak in the 5th-6th decade. A B
Figures A-B: Axial and coronal T2-weighted images with fat saturation, demonstrate a uniformly hyperintense lobulated mass centered within the anterior superior sinonasal cavity, eroding into the suprasellar cistern, cavernous sinus, and right ostiomeatal unit. A mass centered along the cribriform plate, with peritumoral cysts along the superior margin of the mass (), is classic.

23. Esthesioneuroblastoma (2/3)
T1-hypointense and T2-iso/hyperintense relative to brain parenchyma
Moderate enhancement and tumoral cysts along the superior margin is classic.
Ddx: nasopharyngeal carcinoma, adenocarcinoma C D E
Figure 4 (C-E): Mutiplanar T1-weighted images before the administration of intravenous contrast, demonstrate a uniformly T1-hypointense mass filling the ethmoidal and frontal air cells, with obstruction of the sphenoid and right maxillary sinuses. The mass has eroded through the cribriform plate and displaces the orbitofrontal cortex.

24. Esthesioneuroblastoma (3/3)
Kadish System for Staging Esthesioneuroblastoma:
Kadish 1: Limited to the nasal cavity
Kadish 2: Involvement of the paranasal sinuses
Kadish 3: Local extension beyond the nasal cavity and paranasal sinuses
Kadish 4: Distant and/or nodal metastases F G H
Figures F-H: Mutiplanar T1-weighted images following the administration of contrast. The mass is diffusely enhancing, but with preferential hyperenhancement of the tumor margins and relative hypoenhancement of the central mass. There is no abnormal enhancement within the maxillary or sphenoid sinuses, confirming the presence of debris.

25. Pseudotumor Cerebri + Olfactory CSF Leak
45 year old female with chronic headaches, blurry vision, nausea, hyposmia, and rhinorrhea.
Serial coronal T2 weighted images (A-C) and sagittal FIESTA (D) demonstrate cystic outpouching along the bilateral olfactory fossa (), surrounding the olfactory bulbs. On the right side, there is dehiscence of the cribriform plate and CSF opacification of the right olfactory cleft (). There was diffused enlargement of the skull base cisterns, including the sella (), reflective of chronically elevated intracranial pressure.

26. Olfactory Encephalocele
65-year-old male with symptoms of hyposmia and rhinorrhea.
CT cisternogram of the sinuses was performed and demonstrates occlusion of the right olfactory cleft with a meningocele that contains CSF and a prolapsed/herniated olfactory bulb (). The cribriform plate is clearly deficient on the right side ().
This is being considered an encephalocele and not just an meningocele, since the herniated dural sac contains portions of the olfactory tract (a CNS component).

27. Viral Infection
Hyposmia secondary to viral infection is a common entity and really a clinical diagnosis – often one of exclusion. Imaging rarely offers a strong clue to the presence of viral infection in this setting, but is still valuable in ruling out other entities. A B
However, in a patient with a clinical diagnosis of viral-induced hyposmia, we can sometimes see in retrospect slight hyperenhancement of the olfactory epithelium at the level of the cribriform plate. This is a subtle call, and should only be suggested in the appropriate clinical setting.
How much enhancement is too much? Personally, I use the respiratory epithelium of the nasal cavity as an internal reference.
In this case, precontrast (A) and postcontrast (B) T1-weighted imaging suggests hyperenhancement and engorgement of the olfactory epithelium ().

28. Multiple Sclerosis A B
A somewhat unusual case of a patient with known history of multiple sclerosis, presenting with hyposmia in the setting of recent flare.
Axial (A) and coronal (B) volumetric T2 FLAIR postcontrast images with fat supression – demonstrate T2 FLAIR hyperenhancement of the olfactory bulbs (). Olfactory dysfunction is actually a very common yet under-recognized symptom of MS, and has been shown to be associated with decreased volume of the olfactory bulbs and tracts. It is unclear if this is due to secondary effects of damage to the central processing areas of olfaction, or potentially from direct attack of the olfactory bulbs themselves.

29. Neurosarcoidosis
Two different patients with history of sarcoidosis, presenting with dysosmia. A B C
Coronal postcontrast T1-weighted images for the first patient (A-B) demonstrate diffuse leptomeningeal enhancement along the medial orbitofrontal/olfactory cortex () in addition to hyperenhancement of the olfactory bulbs ().
Similar imaging of the second patient (C) also demonstrates hyperenhancement of the olfactory bulbs (), although without the added feature of leptomeningeal enhancement.

30. Olfactory Groove Hemorrhage/Trauma
50-year-old male with 3 week history of phantosmia (smelled natural gas) following sudden onset headed that occurred spontaneously during a heated argument. A B C D E
Subdural and subarachnoid blood products track along the right front convexity down into the olfactory fossae (), surrounding and irritating the olfactory bulbs.
Axial T2 (A), Axial T1 +C (B), axial T2* GRE (C), Sagittal T1 (D), Coronal T2 FLAIR CUBE +C (E).

31. Olfactory Groove Trauma
Remote history of motor vehicle collision, now with anosmia and seizures. A B C
Sagittal T2 FLAIR CUBE (A), axial (B) and coronal (C) T2 weighted images, demonstrate a well-defined area of cystic encephalomalacia with marginal gliosis (), which replaces the right greater than left orbitofrontal cortices. Remarkably, there is relatively preservation of the olfactory bulbs ().

32. Olfactory Bulb Injury A B
Coronal (A) and axial (B) T2 single shot turbo spin echo (HASTE) images of an 1-month-old infant that suffered from severe non-accidental head trauma. In addition to numerous other intracranial injuries, there is conspicuous vacuolization of the olfactory bulbs (), with thinning of the outer neuronal layer.
In newborns, the central portions of the olfactory bulbs may demonstrate T2 hyperintensity that is reflective of unmyelinated fibers, but in this case the bulbs are over expanded and the outer layer is thinner than expected for the patient’s age. Extra-axial blood and orbitofrontal contusions in this region help confirm the pattern of injury (better seen on other imaging, not shown).

33. Olfactory Groove Metastatic MelanomaB E C D
Sagittal and axial precontrast T1-weighted images (A & C) demonstrate a large infiltrative mass with intrinsic T1 hyperintensity that replaces the right orbitofrontal lobe ().
It’s extent is more readily appreciated after the administration of contrast (B,D-E), particularly in the coronal plane (E), which shows the mass extending down into the right olfactory groove and fossa ().

34. Lateral Olfactory Groove Meningioma
Coronal and axial postcontrast T1-weighted images (A-B) demonstrate a large enhancing extra-axial mass that grows along the floor of the right anterior cranial fossa down into the right olfactory fossa ().
Coronal T2 weighted imaging (C) demonstrates the degree of marked mass effect on the right prefrontal lobe as well as edema (). To the left of midline, large peritumoral cysts indent the left prefrontal lobe ().
Sagittal precontrast T1-weighted imaging (D) confirms hyperostosis of the right lateral planum sphenoidale ().
CSF dilatation of the contralateral optic nerve sheath may be present with this entity (“Foster-Kennedy Syndrome”). A B C D

35. Medial Olfactory Groove MeningiomaB C D
Another example of a meningioma involving the orbitofrontal lobes and proximal olfactory tracts, but in this case arising medially.
Sagittal (A) and coronal (B-C) postcontrast T1-weighted imaging demonstrates a large dural based mass arising from the anterior falx cerebri and midline planum sphenoidale, extending from the anterior sella into the olfactory fossa. As is often encountered with this type of presentation, there is tumoral encasement of the anterior cerebral arteries (), which can complicate resection.
Axial T2-weighted imaging (D) shows the degree of mass effect and edema throughout the medial prefrontal lobes.

36. Olfactory Groove Aneurysm
40-year-old male presents with chronic headaches and intermittent blurry vision. On exam, he has difficulty discriminating smells (e.g. peanut butter, orange). A B C D E F
A massive AComm aneurysm with concentric layers of mural thrombus (), correspondingly hyperintense on sagittal/axial T1-weighted images (A, E) and hypointense on axial T2 (F).
On lateral/frontal ICA angiogram images (B-C), only the center portion of the aneurysm mass opacifies with contrast ().
Coronal postcontrast T1 imaging (D) confirms this small pocket of filling (), as well as enhancement of the wall () – a worrisome sign for shear stress.

37. Alzheimer’s Disease A B B C D E F
T2 FLAIR weighted imaging in the axial (A) and coronal (C) planes demonstrate disproportionate prominence of the temporal horns () secondary to hippocampal atrophy.
On corresponding PET imaging with F-18 radiolabeled florbetapir (beta-amyloid binding agent), reconstructed in the axial and coronal planes (B and D) -- there is markedly increased uptake of radiopharmaceutical throughout the the cerebral cortices, particularly the frontal and temporal regions.
For comparison, axial and coronal F-18 florbetapir images from a patient without Alzheimer’s disease (E-F) is shown at the bottom left; there is normal distribution of radiopharmaceutical throughout the cerebral white matter, with relative sparing of the cortex and overall less uptake. E F

38. Question #3: Which of the following is TRUE regarding olfactory dysfunction in Alzheimer’s Disease (AD)?
Hyposmia correlates with the degree of tau-protein deposition and neurofibrillary tangles within the olfactory bulbs.
Apolipoprotein E (ApoE) ε4 positive-status correlates with increased olfactory dysfunction and worse clinical severity of AD.
Decreased olfactory identification and perception is a predictor of clinical severity of AD and onset of cognitive decline.
Olfactory deficits correlate with neurodegeneration of the lateral olfactory pathway.
All of the above.

39. Question #3: Which of the following is TRUE regarding olfactory dysfunction in Alzheimer’s Disease (AD)?
Hyposmia correlates with the degree of tau-protein deposition and neurofibrillary tangles within the olfactory bulbs.
Apolipoprotein E (ApoE) ε4 positive-status correlates with increased olfactory dysfunction and worse clinical severity of AD.
Decreased olfactory identification and perception is a predictor of clinical severity of AD and onset of cognitive decline.
Olfactory deficits correlate with neurodegeneration of the lateral olfactory pathway.
All of the above.

40. Parkinson’s Disease A B C
A: Serial SPECT images from a I-123 Ioflupane (DaTSCAN) study demonstrate decreased uptake within the striatum, moreso on the right side (), which is consistent with the clinical diagnosis of Parkinson Disease (PD).
B: Transverse SPECT I-123 Ioflupan image from another patient with tremor and incidentally noted hyposmia. This also shows markedly decreased uptake in the bilateral striatum (), confirming PD. For comparison, a scan from a normal patient is shown (C).
I-123 Ioflupane is a radiopharmaceutical that binds to presynaptic dopamine transporters. Although it has been shown that there are paradoxically increased dopaminergic cells in the olfactory bulbs of PD patients, this is not visible on our current studies. B C
Hyposmia has been demonstrated to be a common feature of early PD and can predate the onset of motor symptoms, potentially helping distinguish it from other causes of tremor.

41. Epilepsy - Mesial Temporal SclerosisB C
A-C: Studies from a patient with MTS and olfactory aura.
Coronal T2-weighted imaging (A) demonstrates small size and T2 hyperintensity of the left hippocampus ().
On Tc-99m Ceretec SPECT scans reconstructed in the coronal (B) and axial (C) planes during the ictal phase, there is corresponding decreased radiotracer uptake in the left hippocampal formation (), but increased radiotracer uptake in the left insular cortex () – the latter finding is highly suggestive of a putative epileptogenic focus.
D: A second patient with right-sided mesial temporal sclerosis.
FDG-PET scan demonstrates decreased metabolic activity in the right temporal and parietal lobes (). D

42. Temporal Lobe Glioma A B C
55-year-old male presents with headache and olfactory hallucinations. A B C
Sagittal T1-weighted imaging (A) demonstrates a hemorrhagic cavity with intrinsic T1 hyperintense blood products (), centered along the ventral margin of the left temporal lobe.
Corresponding sagittal and axial T2 FLAIR weighted imaging (B-C) demonstrates confluent expansile areas of nonenhancing tumor infiltrating the majority of the left medial temporal lobe (), in addition to a small amount of superimposed perihemorrhagic vasogenic edema.
Pathology confirmed high-grade (WHO grade IV) glioma, with intralesional hemorrhage. In this case, the lateral olfactory pathway is primarily involved, which is important for the recognition of odors (memory) as well as assigning an emotional valence to the stimulus (limbic).

43. Temporal Lobe Metastasis
Patient with history of truncal cutaneous melanoma, presents with seizure and olfactory aura. A B C D
Axial T1 (A), T1+C (B), T2 (C), and T2*GRE (D) weighted images demonstrate marked expansion of the right temporal lobe with a complex cystic mass lesion with peripheral enhancement and internal proteinaceous contents.
Of note, the lateral margin of the mass possess nodular implants with intrinsic T1 hyperintensity () and associated T2* blooming (), consistent with the paramagnetic effects of melanin. These metastases are prone to hemorrhage, as demonstrated by the hematocrit layer within the dependent portion of the cavity ().

44. In Summary
Normal olfaction depends on the interaction of several intact physiologic processes, including: normal transmission of odorants to the olfactory epithelium (conductive), normal receptor interaction and olfactory signal transduction (sensorineural), and appropriate processing of olfactory stimuli via multiple CNS pathways (central).
Olfactory disturbances can arise from a wide range of conditions, including disorders of the sinonasal cavities, olfactory nerves/bulbs, and CNS.
Olfactory deficits/derangements may be an early sign of CNS disease, including multiple neurodegenerative conditions (Alzheimer’s, Parkinson’s, MS, etc..). Imaging can be helpful for characterizing putative lesions as well as excluding worrisome conditions.

45. References/Suggested Reading
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46. Thank you!