- Open Access
Diffusion tensor imaging: a smart move to olfactory pathway imaging; comparative study of chronic sinonasal polyposis patients and normal control
Egyptian Journal of Radiology and Nuclear Medicine volume 51, Article number: 34 (2020)
Olfaction is critically important for a good quality of life and incorporated in many physiological domains such as attention, emotion, memory, and airflow motor control. Olfactory researches have been expanded in the last decade due to close relation between the olfactory disorders and different brain diseases. Diagnosis of anosmia and hyposmia are based on history, smell tests, and physical examination which rely on the patient’s response without an objective measure of impairment. This study assessed the value of volumetry and DTI parameters as objective measurements for olfactory dysfunction.
Fourteen patients with chronic sinonasal polyposis for at least 6 months were included in this study; all of them underwent tailored MRI examination including volumetry and DTI for olfactory bulbs and tracts. The results were compared to the same number of age and sex-matched healthy control group.
The study results showed that olfactory bulb and tract (OB/T) volume, FA and ADC could distinguish between patients and healthy controls. Statistically significant differences were noticed between the FA & ADC values of patient and control groups (p < 0.05) and a highly significant one was noticed as regarding the OT volume (p < 0.001).
MR volumetry and DTI parameters can be used as objective measurements for the olfactory dysfunction for patients with chronic sinonasal polyposis.
Although olfaction is critically important for a good quality of life, personal safety, and nutritional status, the sense of smell is substantially underlooked . The prevalence of olfactory disorders is quite high in population-based studies in which odor identification has been assessed. In a Swedish study, 19% of the adult population was found to have some kind of dysfunction in the sense of olfaction . Many factors influence the normal ability to smell. In patients presenting in otorhinolaryngological clinics, approximately 70% of all patients presenting with chronic hyposmia or anosmia attribute that to sinonasal causes (of which, polyposis account for 14% to 30%) [3,4,5,6], 10% are due to post-infectious inflammation of the mucosa, 1% have congenital anosmia, while the rest have a central cause for their anosmia (i.e., trauma; tumors; toxicity; or psychiatric, neurodegenerative, or another neurologic etiology) [7, 8]. Correct assessment of the cause of olfactory impairment is important to determine which patients may benefit from therapy. It helps in the counseling of patients [4, 9, 10]. Conservative therapy with corticosteroids as well as surgical therapy have been proven to be effective in the treatment of sinonasal disease-related olfactory disorders but not non-sinonasal disease [11, 12]. Olfactory research has expanded rapidly over the last two decades, owing to the close relationship between anosmia and brain disease. Hyposmia and anosmia were identified as a prodromal symptom of Parkinson’s disease (PD), as strong predictors of cognitive decline in Alzheimer’s disease, and have been found to be closely related to depression [13,14,15,16,17,18]. Clinicians diagnose anosmia through history, physical examination, and smell tests  which depend entirely on patient responses. The available smell identification test may enable us to identify and diagnose olfactory dysfunction, but it does delineate central from peripheral causes.
Recently, efforts have been made to use neuroimaging of the olfactory tract and bulbs to refine the diagnosis of olfactory dysfunction. The measurement of olfactory bulb and tract (OB/T) by planimetric manual contouring on magnetic resonance imaging (MRI) correlated well with olfactory function [20, 21]. However, these thin structures are difficult to measure with significant variations among healthy individuals rendering its efficiency as a diagnostic tool limited [4, 5, 22].
Diffusion tensor imaging (DTI) is a non-invasive technique that is gaining popularity since it enables the delineation of white matter tracts as well as their connectivity of different brain areas . It has been integrated in the evaluation of cranial nerves including the olfactory nerve, which has been a matter of study in both the normal and abnormal populations .
DTI studies of individuals with Parkinson’s disease revealed a correlation between reduced fractional anisotropy (FA) values in the olfactory bulb and anosmia [25, 26]. Recently, several studies pointed out the capacity of DTI parameters of revealing brain tissue damage in early clinical stages of neurodegenerative diseases [26,27,28].
To the best of our knowledge, this is the first work that compares OB/T volume and DTI parameters in patients with sinonasal polyposis as opposed to healthy controls.
The aim of this study was to evaluate the effect of olfactory deprivation caused by sinonasal polyposis on olfactory bulb volume and tract integrity.
This prospective study was carried out between January 2016 and July 2017. The study was approved by the institutional ethical committee and an informed consent was taken from all participants.
Twenty-eight subjects were included in this study: 14 adult patients who had a history of chronic nasal obstruction for more than 6 months who were diagnosed clinically with bilateral allergic sinonasal polyposis (patient group) and 14 healthy adults—matched for age and sex—with no history of olfactory dysfunction or sinonasal problems (control group). Patients who underwent biopsy or surgery; were previously treated; and have sinonasal neoplastic lesions, neurological disorders, or diabetes were excluded. All participants had MRI with DTI.
MR image acquisition
The study was performed on A 1.5-T MR unit (Gyroscan Achieva; Philips Medical Systems, The Netherlands). A tailored protocol was performed by selecting sequences from routine MR of PNS protocol including axial and coronal T2 STIR with 3-mm slice thickness, small field of view (FOV) that extends from the nasal tip to the brainstem (coronal plane) and from the superior border of the frontal sinus to the lower lip (axial plane). Three-dimensional DRIVE was added in coronal plane with slice thickness 0.8 mm, repetition time (TR) 12–15 s. echo time (TE) 6–7 s. matrix 384 × 320, and NEX 1 for accurate localization of the olfactory nerve (Figs. 1b, 2a and 3a).
DT imaging data were acquired by using a single-shot echoplanar imaging sequence with the sensitivity encoding or SENSE, parallel-imaging scheme (reduction factor, 2). The imaging matrix was 128 × 128, with an FOV of 220 × 220 mm. Transverse sections of 2.75-mm thickness acquired parallel to the anterior commissural–posterior commissural line was taken to cover the entire hemisphere and brainstem without gaps. Diffusion weighting was encoded along 12 independent orientations, with b value of 1000 mm2/s. Other imaging parameters were as follows: TE = 70 ms, TR = 6599–8280 ms, and number of acquisitions = 2. Co-registered magnetization-prepared rapid gradient-echo (MPRAGE) images of the same resolution were recorded for anatomic guidance. The total imaging time for DTI was 7–9 min according to the section numbers, which was added to the routine MR imaging examinations.
We transferred the diffusion tensor imaging data to an offline workstation (extended workspace “EWS”; Release 18.104.22.168; Dell, Round Rock, Tx); Pride software (Philips Medical Systems).
FA and apparent diffusion coefficient (ADC) were taken by using a multiple region-of-interest (ROI) approach, where our ROI was the olfactory bulbs and tract on either side from the point of appearance superior to the nasal mucosa, moving posteriorly till they are last visualized (Fig. 3c).
Data were analyzed using Stata® version 14.2 (Stata Corp LLC, College Station, TX, USA). Normality of numerical data distribution was examined using the Shapiro-Wilk test. Non-normally distributed numerical data were presented as median and interquartile range and intergroup differences were compared using the Wilcoxon rank sum test. Correlations were tested using the Spearman rank correlation. Receiver-operating characteristic (ROC) curve analysis was used to examine the diagnostic value of volumetry, FA, or ADC. The DeLong method was used to compare the areas under different ROC curve (AUC). p value < 0.05 was considered statistically significant.
Fourteen patients were included in this study. Their age ranged from 27 to 45 years (median 34). There were 10 males (71.4%) and 4 females (28.6%); 11 patients (78.6%) were anosmic and 3 patients (21.4%) were hyposmic. The control group consisted of 14 healthy volunteers. There were 10 men (71.4%) and 4 women (28.6%), with an age range of 23 to 47 years (median 33).
Using the ROC curve analysis, OB/T volume, FA, and ADC, with values of ≤ 0.054 cm3, ≤ 0.357, and ≥ 1.417 (× 10-3 mm2/s), respectively, were found to be a plausible cutoff point for discrimination between cases and controls (Table 1).
In the patient group, OB/T volume measurements in both sides ranged from 0.0235 to 0.05025 cm3 (median 0.039 cm3). The FA value ranged from 0.27425 to 0.423 (median 0.3495), while ADC value (× 10-3 mm2/s) ranged from 0.98725 to 1.63 (median 1.0414).
In the control group, OB/T volume measurements in both sides ranged from 0.09325 to 0.25125 cm3 (median 0.16 cm3). The FA value ranged from 0.35775 to 0.40225 (median 0.3865), while ADC value (× 10-3 mm2/s) ranged from 0.86925 to 1.299 (median 1.0595; Table 2).
The difference in OB/T volume between patient and control groups was highly statistically significant (p < 0.001), where the patient group had significantly smaller volumes than the control group (Fig. 4). Also, there were statistically significant differences in FA and ADC values between patients and control group (p values = 0.2144 and 0.00438, respectively).
The sense of smell directs the intake of airborne agents into the human respiratory system and determines the flavor and palatableness of foods and beverages. Olfaction enhances the quality of life and yet olfactory disorders are neglected by the medical community .
Many studies showed a statistically significant discrepancy in the OB volume between patients with bilateral sinonasal polyposis and healthy controls, in keeping with the findings revealed in experimental studies on animals, in which decreased inputs from the olfactory epithelium resulted in reduction of OB/T volume [30,31,32,33].
DTI is a non-invasive imaging technique that analyzes the diffusion of water molecules within the tissues. The size, arrangement, and myelination of the axons of the white matter of the brain influence the diffusion of water molecules within them. Fractional anisotropy (FA) reflects the diffusion in various directions while ADC reflects the whole diffusion of water molecules, so an intact white matter tract has higher FA and lower ADC values than a structurally disturbed one (Fig. 1b) .
In this study, we integrate 3D DRIVE sequences and DTI to evaluate the effect of olfactory deprivation caused by sinonasal polyposis on OB/T volume and integrity.
In many studies, age proved to be the strongest correlate of smell disorder in healthy persons, having a larger impact than cigarette smoking. Although marked individual differences are present, age-related smell disorder is more severe in men than women [10, 19, 29]. We could not find a correlation between age, sex, and smoking with OB/T volume, FA, and ADC values in our study. This may be attributed to the small sample of patients, small number of female patients, and small numbers of smokers in the study. Future studies with large representative samples are required to further study the effect of these factors.
We did not perform olfactory tests in this study because our patients had nasal obstruction which led to decreased delivery of particles to the olfactory area. Also, we tried to omit the subjective factors in the study.
In our study, the difference in OB/T volume between patient and control groups was highly statistically significant (p < 0.001). This was in accordance with Islam et al.  who reported that there is a significant reduction in OB volume in patients with bilateral sinonasal polyposis when compared with healthy controls. This result supports the findings in experimental animals, in which decreased inputs from the olfactory epithelium lead to reduction of OB volume [17, 30]. Also, Veyseller et al.  reported that diminished OB volume in total laryngectomy patients may be due to the inability to sniff normally, the lack of naso-pulmonary airflow, and complex neural interruptions caused by surgical denervation of the larynx.
Rombaux et al.  found that patients with post-traumatic or post-infectious olfactory loss have smaller OB volume which correlates with poorer recovery of olfactory function. Hence, OB/T volume reduction may not only impair the sense of smell in sinonasal polyposis patients but may also be responsible of hindering olfactory recovery post operatively. On the other hand, Gudziol et al.  reported that the OT volume in patients with chronic rhinosinusitis had increased significantly after 3 months of medical treatment.
Another study found a positive correlation between olfactory deficit and the reduction in OT volume both in patients with Parkinson’s disease (PD) and controls  which is contrary to what Hummel et al., Huissman et al., and Wattendorf et al. [38,39,40] concluded in their study where little or no difference was found between PD patients with anosmia/hyposmia and healthy controls in terms of OT volume.
Similarly, there were statistically significant differences in FA and ADC values between patients with sinonasal polyps and control group (p values 0.2114 and 0.00438, respectively). Also, by using cutoff criterion ≤ 0.05 cm3, ≤ 0.35, and ≥ 1.417 (× 10-3 mm2/s) for OB/T volume, FA, and ADC values, respectively, discrimination between cases and controls could be obtained.
There were several studies that pointed out the capability of the analysis of the ADC and FA computed from DTI to reveal brain tissue damage in early clinical stages of neurodegenerative diseases, particularly PD. These studies found that PD patients could be completely differentiated from the control group based on reduced FA values [26, 40, 41].
Previous studies suggested that head trauma is the most common cause of olfactory dysfunction, accounting for approximately 17% of all cases. Complete anosmia occurs in 5–10% of all head traumas, while an element of olfactory dysfunction in 20–44% of mild traumatic brain injury (TBIs) and 49–56% of moderate to severe TBIs. Of these cases, only 30–40% achieve partial recovery. DTI was used to furnish physical evidence of post-traumatic anosmia. It revealed dis-integrity of olfactory tracts [42,43,44].
The clinical value of imaging in patients with olfactory dysfunction has been controversial. Busaba  concluded that imaging was not needed in a patient with isolated olfactory dysfunction if clinical examination was normal. Mueller et al. , however, concluded that computed tomography (CT) scans are useful to diagnose conductive/inflammatory olfactory dysfunction in patients suspected of non-sinonasal disease. Imaging studies of the brain and paranasal sinuses are often obtained to determine the site and nature of the underlying pathology. Sinonasal CT is the technique of choice for the study of sinonasal structures .
Our study was the first to address the use of DTI as an objective measure of olfactory dysfunction in patients with nasal polyps. In the absence of obvious physical derangement, the diagnosis of olfactory dysfunction relied upon the patients’ subjective reports. DTI can differentiate hyposmic/anosmic patients from controls and has shown to be useful in the evaluation of the central causes of an olfactory dysfunction.
The potential of this methodology thrilled the DTI community; however, it is critical to note that there is no established gold standard to assess the measurement limits and errors in DTI to confirm that the DTI interpretation is correct. So, introduction of several innovative readout strategies will provide better quality of DTI images and results.
There are few limitations in performing DTI of the olfactory region that need to be kept in mind such as susceptibility artifacts, which result from air spaces within sinonasal spaces or dental fillings with metallic materials. Due to the small number of patients, larger studies in different centers are required to confirm the results. Quantitative olfactory tests are recommended to study the correlation between subjective olfactory derangement and objective quantitative measurements. Also, study of the OB/T volumes and DTI parameters in patients with chronic sinonasal polyposis who underwent surgery to correlate between the subsequent expected increase in volume and recovery of olfactory tract integrity would be interesting to study.
OB/T volumetry and DTI (FA and ADC) could be used as objective measurements to evaluate olfactory dysfunction in patients with sinonasal polyposis.
In this study, we conclude the following:
Patients with sinonasal polyposis have a high prevalence of olfactory disorders.
DTI parameters could be used as an objective method to evaluate olfactory tract integrity in patients with sinonasal polyposis.
Decreased olfactory bulb and tract volume is significantly correlated with decreased olfactory sensitivity.
Availability of data and materials
The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Apparent diffusion coefficient
Diffusion tensor imaging
Olfactory bulb and tract
Wilson RS, Schneider JA, Arnold SE, Tang Y, Boyle PA, Bennett DA (2007) Olfactory identification and incidence of mild cognitive impairment in older age. Arch Gen Psychiatry 64:802–808
Brämerson A, Johansson L, Ek L et al (2004) Prevalence of olfactory dysfunction: The Skövde population-based study. Laryngoscope 114(4):733–737
Murphy C, Schubert CR, Cruickshanks KJ et al (2002) Prevalence of olfactory impairment in older adults. JAMA 288(18):2307–2312
Herzallah IR, Askar MD, Amer HS, Ahmed AF, El-Anwar MW, Eesa MH (2013) Olfactory bulb volume changes in patients with sinonasal polyposis. Otolaryngology Head and Neck Surgery 148(4):689–693
Raviv JR, Kern RC (2004) Chronic sinusitis and olfactory dysfunction. Otolaryngol Clin North Am 37:1143–1157
Seiden AM, Duncan HJ (2001) The diagnosis of a conductive olfactory loss. Laryngoscope 111:9–14
Rombaux P, Huart C, Deggouj N, Duprez T, Hummel T (2012) Prognostic value of olfactory bulb volume measurement for recovery in postinfectious and posttraumatic olfactory loss. Otolaryngol Head Neck Surg 147:1136–1141
Lin A, Ross BD, Harris K et al (2005) Efficacy of proton magnetic resonance spectroscopy in neurological diagnosis and neurotherapic decision making. NeuroRx 2(2):197–214
Wrobel BB, Leopold DA (2004) Clinical assessment of patients with smell and taste disorders. Otolaryngol Clin North Am 37(6):1127–1142
Mueller C, Temmel AF, Toth J et al (2006) Computed tomography scans in the evaluation of patients with olfactory dysfunction. Am J Rhinol 20(1):109–112
Ikeda K, Sakurada T, Suzaki Y, Takasaka T (1995) Efficacy of systemic corticosteroid treatment for anosmia with nasal and paranasal sinus disease. Rhinology 33(3):162–165
Wolfensberger M, Hummel T (2002) Anti-inflammatory and surgical therapy of olfactory disorders related to sino-nasal disease. Chem Senses 27(7):617–622
Nicoletti G, Tonon C, Lodi R et al (2008) Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease. Movement Disord 23(16):2370–2376
Ibarretxe-Bilbao N, Zarei M, Junque C et al (2011) Dysfunction of cerebral networks precede recognition memory deficits in early Parkinson's disease. Neuroimage 57(2):589–597
Welge-Lüssen A, Wattendorf E, Schwerdtfeger U et al (2009) Olfactory induced brain activity in Parkinson's disease relates to the expression of event-related potentials-an fMRI study. Neuroscience 162(2):537–543
Westermann B, Wattendorf E, Schwerdtfeger U et al (2008) Functional imaging of the cerebral olfactory system in patients with Parkinson's disease. J Neurol Neurosurg Psychiatry 79(1):19–24
Ibarretxe-Bilbao N, Junque C, Marti MJ et al (2010) Olfactory impairment in Parkinson's disease and white matter abnormalities in central olfactory areas: a voxel-based diffusion tensor imaging study. Mov Disord 25(12):1888–1894
Holbrook EH, Leopold DA (2003) Anosmia: diagnosis and management. Current opinion in otolaryngology & head and neck surgery 11(1):54–60
Hummel T, Smitka M, Puschmann S, Gerber JC, Schaal B, Buschhüter D (2011) Correlation between olfactory bulb volume and olfactory function in children and adolescents. Exp Brain Res 214:285–291
Haehner A, Rodewald A, Gerber JC, Hummel T (2008) Correlation of olfactory function with changes in the volume of the human olfactory bulb. Arch Otolaryngol Head Neck Surg. 134:621–624
Rombaux P, Duprez T, Hummel T (2009) Olfactory bulb volume in the clinical assessment of olfactory dysfunction. Rhinology 47(1):3–9
Skorpil M, Rolheiser T, Robertson H, Sundin A, Svenningsson P (2011) Diffusion tensor fiber tractography of the olfactory tract. Magnetic resonance imaging 29(2):289–292
Torresa CV, Manzanaresb R, Solac RG (2014) Integrating diffusion tensor imaging-based tractography into deep brain stimulation surgery: a review of the literature. Stereotact Funct Neurosurg 92:282–290. https://doi.org/10.1159/000362937
Milardi D, Cacciola A, Calamuneri A et al (2017) The olfactory system revealed non-invasive mapping by using constrained spherical deconvolution tractography in healthy humans. Front. Neuroanat 11:32. https://doi.org/10.3389/fnana.2017.00032
Tessa C, Giannelli M, Della Nave R et al (2008) A whole-brain analysis in de novo Parkinson disease. AJNR 29(4):674–680
Le Bihan D (2003) Looking into the functional architecture of the brain with diffusion MRI. Nature Rev Neurosc 4(6):469–480
Schocke MF, Seppi K, Esterhammer R et al (2004) Trace of diffusion tensor differentiates the Parkinson variant of multiple system atrophy and Parkinson's disease. Neuroimage 21(4):1443–1451
Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli R (2006) Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics 26(Suppl 1):S205–U219
Doty RL, Shaman P, Dann M (1984) Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 32:489–502
Ackerstaf AH, Hilgers FJM, Aarson NK, Balm AJM (1994) Communication, functional disorders and lifestyle changes after total laryngectomy. Clin Otolaryngol 19:295–300
Cummings DM, Knab BR, Brunjes PC (1997) Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domestica. J Neurobiol 33:429–438
Mandairon N, Sacquet J, Jourdan F, Didier A (2006) Long-term fate and distribution of newborn cells in the adult mouse olfactory bulb: influences of olfactory deprivation. Neuroscience 141:443–451
Veyseller B, Aksoy F, Yildirim YS et al (2011) Reduced olfactory bulb volume in total laryngectomy patients: a magnetic resonance imaging study. Rhinology 49:112–116
Skorpil M, Rolheiser T, Robertson H, Sundin A, Svenningsson P (2010) Diffusion tensor fiber tractography of the olfactory tract. Magn Reson Imaging 29:289–292. https://doi.org/10.1016/j.mri.2010.07.004
Rombaux P, Potier H, Bertrand B, Duprez T, Hummel T (2008) Olfactory bulb volume in patients with sinonasal disease. Am J Rhinol. 22:598–601
Gudziol V, Buschhüter D, Abolmaali N, Gerber J, Rombaux P, Hummel T (2009) Increasing olfactory bulb volume due to treatment of chronic rhinosinusitis: a longitudinal study. Brain 132:3096–3101
Wang J, You H, Liu JF, Zhang ZX, Guan J (2011) Association of olfactory bulb volume and olfactory sulcus depth with olfactory function in patients with Parkinson disease. AJNR 32(4):677–681
Hummel T, Witt M, Reichmann H et al (2010) Immunohistochemical, volumetric, and functional neuroimaging studies in patients with idiopathic Parkinson's disease. J Neurological Sci 298(1-2):119–122
Huisman E, Uylings HB, Hoogland PV (2004) A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in Parkinson's disease. Mov Disord. 19(6):687–692
Wattendorf E, Welge-Lüssen A, Fiedler K et al (2009) Olfactory impairment predicts brain atrophy in Parkinson's disease. J Neurosci. 29(9):15410–15413
Karagulle Kendi AT, Lehericy S, Luciana M, Ugurbil K, Tuite P (2008) Altered diffusion in the frontal lobe in Parkinson disease. AJNR 38(3):501–505
Yousem DM, Geckle RJ, Bilker WB, Kroger H, Doty RL (1999) Posttraumatic smell loss: relationship of psychophysical tests and volumes of the olfactory bulbs and tracts and the temporal lobes. Academic radiology 6(5):264–272
Schofield PW, Moore TM, Gardner A (2014) Traumatic brain injury and olfaction: a systematic review. Front neurol 5:5
Doty RL, Yousem DM, Pham LT, Kreshak AA, Geckle R, Lee WW (1997) Olfactory dysfunction in patients with head trauma. Archives of Neurology 54(9):1131–1140
Busaba NY (2001) Is imaging necessary in the evaluation of the patient with an isolated complaint of anosmia? Ear Nose Throat J 80(12):892–896
Li C, Yousem DM, Doty RL, Kennedy DW (1994) Neuroimaging in patients with olfactory dysfunction. Am J Roentgenol 162:411–418
This study had no funding from any resource.
Ethics approval and consent to participate
The study was approved by the institutional ethical committee (Faculty of Medicine, Ain Shams University Ethical Committee), the committee’s reference number is not applicable. The informed consent obtained from study participants was verbal as all the procedures are noninvasive, so written consent was not required by the institutional ethical committee.
Consent for publication
All patients included in this research gave written informed consent to publish the data contained within the study. If the patient was less than 16 years old, deceased, or unconscious when consent for publication was requested, written informed consent for the publication of this data was given by the parents or legal guardian.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Taha, T., Megahed, A.A., Taha, M.S. et al. Diffusion tensor imaging: a smart move to olfactory pathway imaging; comparative study of chronic sinonasal polyposis patients and normal control. Egypt J Radiol Nucl Med 51, 34 (2020). https://doi.org/10.1186/s43055-020-0140-6