American Association of Endocrine Surgeons| Volume 128, ISSUE 6, P1088-1101, December 2000

A novel, noninvasive imaging technique for intraoperative assessment of parathyroid glands: Confocal reflectance microscopy


      Background. Successful surgical management of primary hyperparathyroidism requires the ability to identify and distinguish normal from abnormal parathyroid tissue. Microscopic pathologic confirmation often helps with the diagnoses and decisions regarding the extent of parathyroid resection. Confocal reflectance microscopy (CRM) is an optical method of noninvasively imaging tissue without fixation, sectioning, and staining as in standard histopathology. The goal of this study was to determine if CRM imaging could be used to distinguish normal from diseased parathyroid tissue intraoperatively. Methods. In this study, 44 parathyroid glands from 21 patients undergoing operations for primary hyperparathyroidism were imaged immediately after excision. CRM images were compared with conventional hematoxylin-and-eosin stained sections obtained from the same gland. The percentage area occupied by fat cells was calculated in images of both normal and diseased glands. Results. Characteristic microscopic features of parathyroid glands were distinguishable by CRM and correlated well with histopathology. The stromal fat content of normal and diseased glands could easily be determined. The percentage area occupied by fat cells differed significantly (P <.00001) in normal glands (average, 23.0% ± 10.9%) and adenomatous glands (average, 0.4% ± 0.7%). Conclusions. CRM imaging rapidly revealed microscopic features that reliably differentiated normal and diseased parathyroid glands. The success of this preliminary ex vivo study promotes interest in further development of an in situ probe for in vivo clinical diagnostic use. (Surgery 2000;128:1088-1101.)
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        • Nussbaum SR
        • Thompson AR
        • Hutcheson KA
        • Gaz RD
        • Wang CA
        Intraoperative measurement of parathyroid hormone in the surgical management of hyperparathyroidism.
        Surgery. 1988; 104: 1121-1127
        • Proye CA
        • Carnaille B
        • Bizzard JP
        • Quievreux JL
        • Leconte-Houcke M
        Multiglandular disease in seemingly sporadic primary hyperparathyroidism revisited: where are we in the early 1990s? A plea against unilateral parathyroid exploration.
        Surgery. 1992; 112: 1118-1122
        • Kaplan EL
        • Bartleff S
        • Sugimoto J
        • Fredland A
        Relation of post-op hypocalcemia to operative technique: deleterious effect of excessive use of parathyroid biopsy.
        Surgery. 1982; 92: 827-834
        • Murphy C
        • Norman J
        The 20% rule: a simple, instantaneous radioactivity measurement defines cure and allows elimination of frozen sections and hormone assays during parathyroidectomy.
        Surgery. 1999; 126: 1023-1029
      1. Atlas of Tumor Pathology, Second Series, Fascicle 14. : Armed Forces Institute of Pathology, Washington, DC1978
        • Webb RH
        Confocal optical microscopy.
        Rep Prog Phys. 1996; 59: 427-471
        • Rajadhyaksha M
        • Grossman M
        • Esterowitz D
        • Webb RH
        • Anderson RR
        In vivo confocal scanning laser microscopy of human skin: melanin provides strong contrast.
        J Invest Dermatol. 1995; 104: 946-952
        • Koenig F
        • González S
        • White WM
        • Lein M
        • Rajadhyaksha M
        Near-infrared confocal laser scanning microscopy of bladder tissue in vivo.
        Urology. 1999; 53: 853-857
        • Boyde A
        • Wolfe LA
        • Maly M
        • Jones SJ
        Vital confocal microscopy in bone.
        Scanning. 1995; 17: 72-85
        • New KC
        • Petroll WM
        • Boyde A
        • Martin L
        • Corcuff P
        • Leveque JL
        • et al.
        In vivo imaging of human teeth and skin using real-time confocal microscopy.
        Scanning. 1991; 13: 369-372
        • Andrews PM
        • Petroll WM
        • Cavanagh HD
        • Jester JV
        Tandem scanning confocal microscopy of normal and ischemic living kidneys.
        Am J Anat. 1991; 191: 95-102
        • Webb RH
        • Hughes GW
        • Delori FC
        Confocal scanning laser ophthalmoscope.
        Appl Optics. 1987; 26: 1492-1499
        • Cavanagh HD
        • Petroll WM
        • Alizadeh H
        • He YG
        • McCulley JP
        • Jester JV
        Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease.
        Ophthalmology. 1993; 100: 1444-1454
        • Sunness JS
        • Schuchard RA
        • Shen N
        • Rubin GS
        • Dagnelie G
        • Haselwood DM
        Landmark-driven fundus perimetry using the scanning laser ophthalmoscope.
        Invest Ophthalmol Vis Sci. 1995; 36: 1863-1874
        • González S
        • White WM
        • Rajadhyaksha M
        • Anderson RR
        • González E
        Confocal imaging of sebaceous gland hyperplasia in vivo to assess efficacy and mechanism of pulsed dye laser treatment.
        Laser Surg Med. 1999; 25: 8-12
        • White WM
        • Rajadhyaksha M
        • González S
        • Fabian RL
        • Anderson RR
        Noninvasive imaging of human oral mucosa in vivo by confocal reflectance microscopy.
        Laryngoscope. 1999; 109: 1709-1717
        • Dekker A
        • Dunsford HA
        • Geyer SJ
        The normal parathyroid gland at autopsy: the significance of stromal fat in adult patients.
        J Pathol. 1979; 128: 127-132
        • Dufour DR
        • Wilkerson SY
        The normal parathyroid revisited: percentage of stromal fat.
        Hum Pathol. 1982; 13: 717-721
        • Rajadhyaksha M
        • González S
        • Zavislan J
        • Anderson RR
        • Webb RH
        In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology.
        J Invest Dermatol. 1999; 113: 293-303
        • Smithpeter C
        • Dunn A
        • Drezek R
        • Collier T
        • Richards-Kortum R
        Near real time confocal microscopy of cultured amelanotic cells: sources of signal, contrast agents, and limits of contrast.
        J Biomed Optics. 1998; 3: 429-436
        • Wang CA
        Surgical management of primary hyperparathyroidism.
        Curr Probl Surg. 1985; 22: 1-50
        • Roth SI
        • Gallagher MJ
        The rapid identification of “normal” parathyroid glands by the presence of intracellular fat.
        Am J Pathol. 1976; 84: 521-528
        • Wang CA
        • Rieder SV
        A density test for the intraoperative differentiation of parathyroid hyperplasia from neoplasia.
        Ann Surg. 1978; 187: 63-67
        • Darling GE
        • Marx SJ
        • Spiegel AM
        • Aurbach GD
        • Norton JA
        Prospective analysis of intraoperative and postoperative urinary cyclic adenosine 3′,5′-monophosphate levels to predict outcome of patients undergoing reoperations for primary hyperparathyroidism.
        Surgery. 1988; 104: 1128-1136
        • Tearney GJ
        • Webb RH
        • Bouma BE
        Spectrally encoded confocal microscopy.
        Optics Lett. 1998; 23: 1152-1154