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Oral Health Research Institute, Indiana University School of Dentistry, Indiana University Emerging Technologies Center, Suite 222, 351 West Tenth Street, Indianapolis, IN 46202-4119; gstookey{at}iupui.edu
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ABSTRACT |
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 TOP ABSTRACT BACKGROUNDCLINICAL CARIES STUDIESCURRENT STATUSCONCLUSIONSREFERENCES |
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KEY WORDS: caries • detection • quantitative light fluorescence
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BACKGROUND |
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TOPABSTRACTBACKGROUNDCLINICAL CARIES STUDIESCURRENT STATUSCONCLUSIONSREFERENCES |
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For many years, the loss of mineral from the enamel and dentin has been known to alter the optical properties, or visual appearance, of teeth; the commonly cited example of this is the so-called "white spot". During the 1960s and ’70s, there were a few scattered reports regarding the use of the optical properties of the teeth for diagnostic purposes. However, it was not until the early 1980s, when Swedish scientists (Bjelkhagen and Sundström, 1981; Bjelkhagen et al., 1982; Sundström et al., 1985) reported on the laser auto-fluorescence of enamel, that serious efforts began in this area. In 1981, these investigators reported on the use of laser auto-fluorescence for the qualitative assessment of mineral loss. These investigators noted that the use of laser fluorescence with the appropriate filters, rather than normal white light, enhanced the contrast between incipient lesions and sound enamel in vivo. Subsequent investigations (Hafström-Björkman et al., 1992) reported on the use of laser fluorescence for the development of a method for the quantitative assessment of enamel demineralization in vitro, and they noted that it compared favorably with longitudinal microradiography for the measurement of mineral changes in enamel in an in vitro caries model.
Following these initial reports of the direct relationship between the mineral content of the enamel and the optical properties, particularly the fluorescence, substantial research was initiated by several groups of investigators to utilize this phenomenon to characterize the dental caries process using various in vitro, in situ, and in vivo models (Angmar-Månsson and ten Bosch, 1987, 1993; ten Bosch and Angmar-Månsson, 1991; Hafström-Björkman et al., 1992; Øgaard and ten Bosch, 1994; de Josselin de Jong et al., 1995; Angmar-Månsson et al., 1996, 2000; Emami et al., 1996; Al-Khateeb et al., 1997a,b, 1998a, 2000; Ando et al., 1997; Hall et al., 1997; Ferreira Zandoná et al., 1998a, b; Eggertsson et al., 1999; Lagerweij et al., 1999; Shi et al., 2001). The results of these studies clearly served to document the ability of laser or light fluorescence to quantify the amount of mineral loss associated with simulated and natural caries lesions of various sizes and to monitor changes in mineral content associated with both demineralization and remineralization.
During the past few years, several in vivo and in situ studies have been conducted for further development of the quantitative light-induced fluorescence methodology in preparation for controlled clinical trials. However, relatively little information has been reported regarding the use of this methodology to monitor clinical caries or to validate the procedure clinically for the early detection of dental caries. This paper sets out to review the potential application of the method in the clinical trial setting, but technical descriptions of the methodology are outside the scope of this article.
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CLINICAL CARIES STUDIES |
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TOPABSTRACTBACKGROUNDCLINICAL CARIES STUDIESCURRENT STATUSCONCLUSIONSREFERENCES |
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In 1995, de Josselin de Jong and co-workers reported a significant improvement in the instrumentation for determining quantitative laser fluorescence involving the use of a CCD microvideo camera and computerized image analysis. They also demonstrated the reproducibility of this technology for the investigation of caries lesions in situ.
In 1997, Al-Khateeb and co-workers reported (1997a,b) on the use of laser fluorescence to quantify in situ effects of fluoride treatments on the remineralization of enamel lesions. Enamel specimens containing induced lesions were mounted on the buccal surfaces of maxillary first molars in 12 panelists at the initiation of each of three 35-day test periods involving different fluoride regimens. The specimens were removed at weekly intervals for imaging and replaced for continued exposure to the test regimens. From the results of the study, it was concluded that the laser fluorescence methodology permitted the detection of the amount of remineralization that occurred during the weekly intervals with each of the fluoride regimens and that the fluorescence results correlated very well with those observed with microradiography at the conclusion of the test periods.
These investigators subsequently reported (Al-Khateeb et al., 1996, 1998a) the results of a pilot study using quantitative laser fluorescence to monitor changes in caries lesions in seven orthodontic patients with active lesions on the buccal surfaces of 15 teeth observed following the removal of the orthodontic brackets. The lesions were imaged in triplicate initially and at monthly intervals for 1 yr. During this period, the patients were provided instructions about dietary habits and effective oral hygiene, and they were provided a fluoride toothpaste for twice daily use. The results demonstrated that the area of the lesions decreased and that the fluorescence lost was partly regained, indicating that partial remineralization had occurred. These investigators concluded that quantitative laser fluorescence could be used to evaluate caries-preventive measures in caries-prone persons.
Quite recently, the Karolinska team reported (Tranaeus et al., 2001b) on the use of the quantitative light-induced fluorescence method in a randomized six-month clinical trial to evaluate the effect of a fluoride varnish on the remineralization of white-spot lesions in 31 caries-active children from 13 to 15 yrs of age. The primary inclusion criterion was the presence of 2 or more white-spot lesions on the buccal surfaces of bicuspids and molars. Treatments consisted of professional tooth-cleaning at baseline and at six-week intervals throughout the test period. The fluoride varnish was applied to the designated patients at baseline, 1 wk, and each six-week visit. The selected lesions were examined by the fluorescence method at baseline and at six-week intervals. The results indicated that, while both regimens resulted in significant remineralization of the lesions, the fluoride varnish regimen was significantly more effective than the professional cleaning regimen alone. The investigators concluded that the quantitative light fluorescence method is a sensitive clinical method suitable for longitudinal quantification of incipient caries lesions on smooth surfaces.
In February, 1998, we initiated a one-year pilot clinical study in 150 children from 9 to 12 yrs of age residing in a non-fluoridated community in Indiana, and the details of this study have been described previously (Ferreira Zandoná et al., 1999). The primary purpose of this pilot study was to obtain the necessary experiences with the then-available early prototype version of the quantitative light fluorescence (QLF) instrument to facilitate the appropriate design of future clinical trials as well as the further development of this instrumentation. All children were provided with a fluoride dentifrice and were instructed to maintain their normal oral hygiene procedures. Dental examinations were performed on all children at baseline, 4, 8, and 12 mos, with a small subset of children being examined monthly for 6 mos and bi-monthly thereafter. The children brushed their teeth with water immediately prior to each series of examinations. The series of examinations included QLF, an electrical conductance meter (ECM), a conventional clinical examination of assigned quadrants with or without the use of a dental explorer and loupes, digital radiography, and bitewing film radiography. Each type of examination was performed by a single examiner to avoid possible bias, and replicate examinations were randomly performed to assess error rates. In addition, exfoliated teeth were collected and subsequently examined by QLF prior to being sectioned for histologic, microradiographic, and polarized light analyses in 5 different laboratories. The results of these latter validation studies were reported previously (ten Cate et al., 1999).
The results from the QLF examinations (Ferreira Zandoná et al., 1999) are summarized in Fig. 1
. In this graph, the mean loss of fluorescence from baseline with the QLF method observed at each four-month examination following the baseline exams is plotted, and the DMFS increments obtained by the conventional clinical examination procedure at each exam period are included for comparison. The mean of the four-month QLF examinations actually was a negative value compared with the baseline value. However, QLF fluorescence loss values increased at each of the subsequent exam periods, reflecting an increase in caries, and the rate of this increase was reasonably comparable with the DMFS (decayed, missing, or filled surfaces) increment obtained with the conventional visual-tactile examinations. These observations suggest that the two methods were detecting incremental caries in these children at comparable rates during the last 8 mos of the study.
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). Considering the significant contribution of occlusal surfaces to the caries increments in clinical trials, this was an important advance of the technology.
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In addition, several aspects of the QLF technology were identified that would greatly benefit from improvements in the methodology. These areas for further development and improvement included: (a) a visual light source within the handpiece to facilitate a visual examination of the tooth surfaces; (b) the need for an improved system for reproducibly capturing images of the suspicious areas of the tooth surfaces; (c) a method for determining whether the suspicious areas represent areas of active caries; and (d) the need for a more efficient and reproducible method for quantitatively analyzing the detected lesions.
As is well-known, research on the further refinement of the QLF technology has continued, and significant improvements have been made since our 1998 pilot clinical study. A major advancement was the development of a markedly improved video repositioning system (de Josselein de Jong et al., 2000; van der Veen and de Josselin de Jong, 2001) for reproducibly capturing the desired images of lesions at subsequent examination periods. This advancement is now an integral part of the QLF instrumentation.
Recent reports (Al-Khateeb et al., 1998b; van der Veen et al., 1999; Ando et al., 2001a,b) have demonstrated the potential for using dehydration phenomena for determining whether enamel hypocalcifications detected by QLF are, in fact, active caries. Hypocalcified areas are inherently filled oral fluids, essentially water, and the presence of water alters the light-scattering properties of the area compared with sound enamel. Further, the presence of remineralization of the surface layer of an incipient enamel lesion (or white spot) retards the loss of fluid from the hypocalcified area. Since very early demineralized areas do not have a surface layer, it follows that the use of controlled dehydration will result in a rapid loss of fluid and an altered fluorescence pattern that will distinguish the lesion from both sound enamel and remineralized or arrested lesions. Fig. 3 presents two of the graphs (from Ando et al., 2001a,b) that illustrate this relationship and indicate that dehydration for as little as 3 sec may be adequate to identify active early lesions in enamel. In addition to these advances in the QLF technology, de Josselin de Jong and the team of scientists at Inspektor Research Systems, Inc. are making major strides in the area of efficient image analyses. Thus, significant improvements in the QLF technology have been made, or are in progress, since our initial pilot clinical study in 1998.
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CURRENT STATUS |
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TOPABSTRACTBACKGROUNDCLINICAL CARIES STUDIESCURRENT STATUSCONCLUSIONSREFERENCES |
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For this technology to become a viable and practical methodology for the detection and evaluation of caries in routine clinical trials, it appears that three major areas need to be addressed. First, the QLF technology requires further refinement, particularly in relation to the prototype instrumentation used in our initial pilot clinical study. As has been noted, much of this work has already been completed, and the remaining needs are presently being addressed. In terms of timing, it is realistic to believe that these efforts will be completed within the next 12 mos.
Second, the ability of the QLF technology to detect and monitor early caries must be clinically validated (ten Bosch and Angmar-Månsson, 2000). In particular, it must be demonstrated that early lesions or demineralized areas detected by QLF will develop eventually into frank clinical caries, thereby confirming that these identified areas, or so-called early caries lesions, are truly caries, as has already been suggested from in vitro and in situ studies. Supported by a Program Project grant from NIH/NIDCR, clinical studies to address this matter with regard to both primary and secondary caries have been initiated during the past few months at the University of Iowa, Indiana University, and the University of Texas. These studies involve children from 8 to 12 yrs of age with examinations conducted at six-month intervals for at least 2 yrs. New technologies being evaluated are quantitative light fluorescence (QLF) and infra-red laser fluorescence (DIAGNOdent), with a conventional visual examination based on the present non-invasive (i.e., no dental explorer) European procedures. Exfoliated deciduous teeth are being collected for evaluation by polarized light microscopy to validate the caries detection methods.
Third, new clinical test designs must be identified and validated (Kingman, 1999). These designs need to consider the use of incipient lesions or very early lesions as a starting point and acceptance of the quantitative assessment of the impact of a treatment procedure during a reasonable period of time, rather than accepting only frank cavitation as an end-point. As has been recently reported (Tranaeus et al., 2001b), with white-spot lesions as a starting point, it was possible to demonstrate a significant benefit from treatments with a fluoride varnish within 6 mos—in fact, within 6 wks—using only 13 patients with 32 lesions. Not only did this study confirm the benefits that have repeatedly been reported with the use of conventional caries clinical procedures, but also the magnitude of the benefit observed with QLF was comparable with that reported previously. The use of patients with the disease under investigation and the specific assessment of the impact of the treatment on these identified lesions are procedures used in medical research to identify effective treatment procedures. Coupling this test design with the inclusion of initially non-carious but high-caries-risk tooth surfaces would permit the assessment of caries-preventive measures as well as caries treatment measures. A clinical pilot study to test and perfect this study design related to fluoride dose response is presently being initiated at Indiana University with Government support.
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CONCLUSIONS |
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TOPABSTRACTBACKGROUNDCLINICAL CARIES STUDIESCURRENT STATUSCONCLUSIONSREFERENCES |
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FOOTNOTES |
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REFERENCES |
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TOPABSTRACTBACKGROUNDCLINICAL CARIES STUDIESCURRENT STATUSCONCLUSIONSREFERENCES |
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Al-Khateeb S, Oliveby A, de Josselin de Jong E, Angmar-Månsson B (1997a). Laser fluorescence quantification of remineralisation in situ of incipient enamel lesions: influence of fluoride supplements. Caries Res 31:132–140.[ISI][Medline]
Al-Khateeb S, ten Cate JM, Angmar-Månsson B, de Josselin de Jong E, Sundström F, Exterkate RA, et al. (1997b). Quantification of formation and remineralization of artificial enamel lesions with a new portable fluorescence device. Adv Dent Res 11:502–506.[Abstract]
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