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How can a massive training artificial neural network (MTANN) be trained with a small number of cases in the distinction between nodules and vessels in thoracic CT?

RATIONALE AND OBJECTIVES: To demonstrate that a massive training artificial neural network (MTANN) can be adequately trained with a small number of cases in the distinction between nodules and vessels (non-nodules) in thoracic computed tomography (CT) images. MATERIALS AND METHODS: An MTANN is a trainable, highly nonlinear filter consisting of a linear-output multilayer artificial neural network model. For enhancement of nodules and suppression of vessels, we used 10 nodules and 10 non-nodule images as training cases for MTANNs. The MTANN is trained with a large number of input subregions selected from the training cases and the corresponding pixels in teaching images that contain Gaussian distributions for nodules and zero for non-nodules. We trained three MTANNs with different numbers (1, 9, and 361) of training samples (pairs of the subregion and the teaching pixel) selected from the training cases. In order to investigate the basic characteristics of the trained MTANNs, we applied the MTANNs to simulated CT images containing various-sized model nodules (spheres) with different contrasts and various-sized model vessels (cylinders) with different orientations. In addition, we applied the trained MTANNs to nontraining actual clinical cases with 59 nodules and 1,726 non-nodules. RESULTS: In the output images for the simulated CT images by use of the MTANNs trained with small numbers (one and nine) of subregions, model vessels were clearly visible and were not removed; thus, the MTANNs were not trained properly. However, in the output image of the MTANN trained with a large number of subregions, various-sized model nodules with different contrasts were represented by light nodular distributions, whereas various-sized model vessels with different orientations were dark and thus were almost removed. This result indicates that the MTANN was able to learn, from a very small number of actual nodule and non-nodule cases, the distinction between nodules (spherelike objects) and vessels (cylinder-like objects). In nontraining clinical cases, the MTANN was able to distinguish actual nodules from actual vessels in CT images. For 59 actual nodules and 1,726 non-nodules, the performance of the MTANN decreased as the number of training samples (subregions) in each case decreased. CONCLUSIONS: The MTANN can be trained with a very small number of training cases (10 nodules and 10 non-nodules) in the distinction between nodules and non-nodules (vessels) in CT images. Massive training by scanning of training cases to produce a large number of training samples (input subregions and teaching pixels) would contributed to a high generalization ability of the MTANN.

Algorithms↗

Regulation of nodulation in the absence of N2 is different in actinorhizal plants with different infection pathways.

Root nodulation in actinorhizal plants, like Discaria trinervis and Alnus incana, is subject to feedback regulatory mechanisms that control infection by Frankia and nodule development. Nodule pattern in the root system is controlled by an autoregulatory process that is induced soon after inoculation with Frankia. The final number of nodules, as well as nodule biomass in relation to plant biomass, are both modulated by a second mechanism which seems to be related to the N status of the plant. Mature nodules are, in part, involved in the latter process, since nodule excision from the root system releases the inhibition of infection and nodule development. To study the effect of N(2) fixation in this process, nodulated D. trinervis and A. incana plants were incubated under a N(2)-free atmosphere. Discaria trinervis is an intercellularly infected species while A. incana is infected intracellularly, via root hairs. Both symbioses responded with an increment in nodule biomass, but with different strategies. Discaria trinervis increased the biomass of existing nodules without significant development of new nodules, while in A. incana nodule biomass increased due to the development of nodules from new infections, but also from the release of arrested infections. It appears that in D. trinervis nodules there is an additional source for inhibition of new infections and nodule development that is independent of N(2) fixation and nitrogen assimilation. It is proposed here that the intercellular Frankia filaments commonly present in the D. trinervis nodule apex, is the origin for the autoregulatory signals that sustain the blockage of initiated nodule primordia and prevent new roots from infections. When turning to A. incana plants, it seems likely that this signal is related to the early autoregulation of nodulation in A. incana seedlings and is no longer present in mature nodules. Thus, actinorhizal symbioses belonging to relatively distant phylogenetic groups and displaying different infection pathways, show different feedback regulatory processes that control root nodulation by Frankia.

Alnus↗

Composition and Distribution of Adenylates in Soybean (Glycine max L.) Nodule Tissue.

Adenylates (ATP, ADP, and AMP) may play a central role in the regulation of the O2-limited C and N metabolism of soybean nodules. To be able to interpret measurements of adenylate levels in whole nodules and to appreciate the significance of observed changes in adenylates associated with changes in O2-limited metabolism, methods were developed for measuring in vivo levels of adenylate pools in the cortex, plant central zone, and bacteroid fractions of soybean (Glycine max L. Merr cv Maple Arrow x Bradyrhizobium japonicum strain USDA 16) nodules. Intact nodulated roots were either frozen in situ by flushing with prechilled Freon-113(-156[deg]C) or by rapidly (<1 s) uprooting plants and plunging them into liquid N2. The adenylate energy charge (AEC = [ATP + 0.5 x ADP]/[ATP + ADP + AMP]) of whole-nodule tissue (0.65 [plus or minus] 0.01, n = 4) was low compared to that of subtending roots (0.80 [plus or minus] 0.03, n = 4), a finding indicative of hypoxic metabolism in nodules. The cortex and central zone tissues were dissected apart in lyophilized nodules, and AEC values were 0.84 [plus or minus] 0.04 and 0.61 [plus or minus] 0.03, respectively. Although the total adenylate pool in the lyophilized nodules was only 41% of that measured in hydrated tissues, the AEC values were similar, and the lyophilized nodules were assumed to provide useful material for assessing adenylate distribution. The nodule cortex contained 4.4% of whole-nodule adenylates, with 95.6% being located in the central zone. Aqueous fractionation of bacteroids from the plant fraction of whole nodules and the use of marker enzymes or compounds to correct for recovery of bacteroids and cross-contamination of the bacteroid and plant fractions resulted in estimates that 36.2% of the total adenylate pool was in bacteroids, and 59.4% was in the plant fraction of the central zone. These are the first quantitative assessments of adenylate distribution in the plant and bacteroid fractions of legume nodules. These estimates were combined with theoretical calculations of rates of ATP consumption in the cortex (9.5 nmol g-1 fresh weight of nodule s-1), plant central zone (38 nmol g-1 fresh weight of nodule s-1), and bacteroids (62 nmol g-1 fresh weight of nodule s-1) of soybean nodules to estimate the time constants for turnover of the total adenylate pool and the ATP pool within each nodule fraction. The low values for time constant (1.6-5.8 s for total adenylate, 0.9-2.5 s for ATP only) in each fraction reflect the high metabolic activity of soybean nodules and provide a background for further studies of the role of adenylates in O2-limited nodule metabolism.

Journal Article↗

Host recognition in the Rhizobium-soybean symbiosis: detection of a protein factor in soybean root exudate which is involved in the nodulation process.

The mechanism of host-symbiont recognition in the soybean-Rhizobium symbiosis was investigated utilizing mutants of R. japonicum defective in nodulation. Soybeans were grown in clear plastic growth pouches allowing the identification of the area on the root most susceptible to Rhizobium nodulation; the area between the root tip (RT) and smallest emergent root hair (SERH). The location of nodules in relation to this developing zone is an indication of the rate of nodule initiation. Nodules were scored as to the distance from the RT mark made at the time of inoculation. Seventy-eight per cent of the plants nodulate above the RT mark when inoculated with the wild type R. japonicum strain 3I1b110 with the average distance of the uppermost nodule being approximately 2 millimeters above the RT mark. These data indicate that the wild type strain initiates nodulation rapidly within the RT-SERH zone following inoculation. However, inoculation with the slow-to-nodulate mutant strain HS111 resulted in 100% of the plants nodulating only below the RT mark with the average distance of the uppermost nodule being approximately 56 millimeters below the RT mark. Thus, mutant strain HS111 is defective in the ability to rapidly initiate infection leading to nodulation within the RT-SERH zone. The location of the nodules suggest that stain HS111 must ;adapt' to the root environment before nodulation can occur. To test this, strain HS111 was incubated in soybean root exudate prior to inoculation. In this case, 68% of the plants nodulated above the RT mark with the average distance of the uppermost nodule being approximately 1 millimeter below the RT mark. Experiments indicated that the change in nodule initiation by strain HS111 brought about by incubation in soybean root exudate was due to a phenotypic, rather than a genotypic change. The half-time of root exudate incubation for strain HS111 necessary for optimal nodulation enhancement was less than 6 hours. Heat sensitivity and trypsin sensitivity of the nodulation enhancement factor(s) in soybean root exudate indicate a protein was involved in the reversal of the delay in nodulation by mutant strain HS111.

Journal Article↗

Small pulmonary nodules: reproducibility of three-dimensional volumetric measurement and estimation of time to follow-up CT.

PURPOSE: To determine reproducibility of volume measurements of small pulmonary nodules on computed tomographic (CT) scans and to estimate critical time to follow-up CT. MATERIALS AND METHODS: One hundred fifteen pulmonary nodules for which two thin-section small-field-of-view CT scans were obtained and which were stable during 2-year observation were evaluated. A standard group of 94 nodules (with no or minimal artifact) and an expanded group of 105 nodules (including those with moderate artifacts) were examined. Percentage volume change (PVC) and monthly volumetric growth index (MVGI) were computed for each nodule pair. By using estimates of the variation in PVC in stable nodules as a function of initial diameter, critical time to follow-up CT was estimated; this time is the earliest point at which growth in a nodule of a given size can be reliably identified with repeat CT. RESULTS: The SD of PVC decreased with increasing nodule size from 18.5% in 2-5-mm nodules to 10.6% in 5-8-mm nodules and to 7.47% in 8-10-mm nodules. Inclusion of cases with moderate motion artifacts increased the SD of PVC to 27.4% in 2-5-mm nodules, to 17.1% in 5-8-mm nodules, and to 19.3% in 8-10-mm nodules. Critical time to follow-up CT for nodules detected at baseline screening was 12, 5, and 3 months and 1 month for those with initial sizes of 2, 5, 8, and 10 mm, respectively. For nodules detected at annual repeat screening, it was 4 and 3 months and 1 month for nodules that were 3, 4, and 5 mm or larger in size, respectively. Mean MVGI in 94 standard cases was 0.06%, and standard error was 0.21%. CONCLUSION: Factors that affect reproducibility of nodule volume measurements and critical time to follow-up CT include nodule size at detection, type of scan (baseline or annual repeat) on which the nodule is detected, and presence of patient-induced artifacts.

Artifacts↗

Solitary thyroid nodule. Comparison between palpation and ultrasonography.

OBJECTIVE: To determine the accuracy of clinical palpation in the diagnosis of solitary thyroid nodule in comparison with ultrasonographic findings. METHODS: From a computerized database of 1774 patients with the diagnosis of nodular thyroid disease made from January 1990 through December 1991 at our institution, we retrieved and reviewed the medical records of the 193 patients who underwent ultrasonography of the thyroid (42 patients with multinodular glands on palpation were excluded). Nodules were categorized as "solitary" or "dominant nodule of a multinodular gland." Concordance rates were measured between results of palpation and ultrasonographic findings. RESULTS: Of 151 patients included in the study, 78 had solitary nodules on ultrasonography and 73 had multiple nodules. Of those with multiple nodules, 49 had two nodules and 24 had three or more nodules. Of clinically palpable nodules, 89% were 1 cm or greater in diameter. In 72% of the patients with multiple nodules, the other nodules not identified on palpation were less than 1 cm in diameter. The overall concordance rate between the size of the solitary nodule or the dominant nodule in a multinodular gland estimated with clinical palpation and the actual size seen on ultrasonography was 72%. The relationship between multiple nodules and malignancy was not statistically significant. CONCLUSIONS: Our results suggest that (1) a palpable solitary nodule represents a multinodular gland in about 50% of patients, (2) clinical palpation is less sensitive than thyroid ultrasonography in identifying multiple nodules, and (3) palpation is reliable only if a nodule is at least 1 cm in diameter. We recommend that small, occult (impalpable) thyroid nodules not be considered clinically important; they do not warrant further evaluation unless ultrasonographic features suggest malignancy or the nodule increases in size.

Adult↗

Computer-aided diagnostic scheme for distinction between benign and malignant nodules in thoracic low-dose CT by use of massive training artificial neural network.

Low-dose helical computed tomography (LDCT) is being applied as a modality for lung cancer screening. It may be difficult, however, for radiologists to distinguish malignant from benign nodules in LDCT. Our purpose in this study was to develop a computer-aided diagnostic (CAD) scheme for distinction between benign and malignant nodules in LDCT scans by use of a massive training artificial neural network (MTANN). The MTANN is a trainable, highly nonlinear filter based on an artificial neural network. To distinguish malignant nodules from six different types of benign nodules, we developed multiple MTANNs (multi-MTANN) consisting of six expert MTANNs that are arranged in parallel. Each of the MTANNs was trained by use of input CT images and teaching images containing the estimate of the distribution for the "likelihood of being a malignant nodule," i.e., the teaching image for a malignant nodule contains a two-dimensional Gaussian distribution and that for a benign nodule contains zero. Each MTANN was trained independently with ten typical malignant nodules and ten benign nodules from each of the six types. The outputs of the six MTANNs were combined by use of an integration ANN such that the six types of benign nodules could be distinguished from malignant nodules. After training of the integration ANN, our scheme provided a value related to the "likelihood of malignancy" of a nodule, i.e., a higher value indicates a malignant nodule, and a lower value indicates a benign nodule. Our database consisted of 76 primary lung cancers in 73 patients and 413 benign nodules in 342 patients, which were obtained from a lung cancer screening program on 7847 screenees with LDCT for three years in Nagano, Japan. The performance of our scheme for distinction between benign and malignant nodules was evaluated by use of receiver operating characteristic (ROC) analysis. Our scheme achieved an Az (area under the ROC curve) value of 0.882 in a round-robin test. Our scheme correctly identified 100% (76/76) of malignant nodules as malignant, whereas 48% (200/413) of benign nodules were identified correctly as benign. Therefore, our scheme may be useful in assisting radiologists in the diagnosis of lung nodules in LDCT.

Algorithms↗

Controversies in the management of cold, hot, and occult thyroid nodules.

Some aspects of thyroid nodule evaluation and management remain controversial. Radionuclide scanning provides functional information about nodules and differentiates cold from hot nodules. Although thyroid cancers are cold on scan, most cold nodules are benign. Ultrasonography visualizes the thyroid gland and nodules with remarkable clarity and provides structural information about location, number, size, and consistency of nodules. Widespread application of ultrasonography has resulted in the frequent discovery of incidental (occult) nodules in the general population. The clinical significance of these nodules remains unknown, and their management has created a dilemma for physicians. Current cost-effective evaluation of nodules does not include scanning or ultrasonography as routine frontline tests. In most centers, fine-needle aspiration biopsy has supplanted imaging studies as the routine initial procedure for differentiating benign from malignant nodules. Cytologic diagnosis is reliable and inexpensive, and it results in a better selection of patients for surgery. Limitations include false-negative diagnoses, nondiagnostic results, and indeterminate "suspicious" results. Laboratory test results are usually normal, but determination of serum thyrotropin may identify a hot nodule, and plasma calcitonin may help diagnose medullary thyroid carcinoma. Treatment of thyroid nodules is controversial. In some practices, benign colloid nodules are treated with suppressive doses of levothyroxine. Recent reports cast doubt on the efficacy of this approach, and it is no longer acceptable to select patients for surgical treatment on the basis of suppressive therapy. Furthermore, suppressive levothyroxine therapy may be associated with significant bone and cardiac side effects, especially in elderly patients and postmenopausal women. Our approach is observation for most patients, and we suggest a careful risk-benefit analysis when suppression is considered. Hot (autonomous) nodules can be treated with radioiodine, surgery, or ethanol injection. The use of sensitive thyrotropin assays has revealed that the "euthyroid" hot nodule is often associated with subclinical hyperthyroidism, warranting treatment if risks of osteoporosis are significant. Small (< 1.5 cm) occult nodules can be observed. Larger (> 1.5 cm) nodules can be selectively evaluated by ultrasonographically guided fine-needle aspiration. It is prudent to consider cost of care, risk-benefit analysis, and the low incidence of malignancy in thyroid nodules when diagnostic tests are selected and the treatment plan is outlined.

Biopsy, Needle↗

Peripheral solitary pulmonary nodule: CT findings in patients with pulmonary emphysema.

PURPOSE: To analyze retrospectively the computed tomographic (CT) features of peripheral noncalcified solitary pulmonary nodules in patients with and those without emphysema. MATERIALS AND METHODS: The authors' institutional review board required neither its approval nor patient informed consent for this retrospective study. The authors retrospectively reviewed 2-mm-thick CT images of 41 nodules (21 malignant, 20 benign) in 41 patients with emphysema (age range, 58-88 years; mean, 71.9 years) and 40 nodules (20 malignant, 20 benign) in 40 patients without emphysema (age range, 50-85 years; mean, 69.2 years). Two radiologists who were unaware of the diagnosis independently evaluated the shape and margin of the nodule, recorded the presence of ground-glass opacities and air bronchograms, and classified nodules into two diagnostic categories: malignant and benign. Final decisions were reached by consensus. For quantitative assessment of the nodules, the fractal dimensions of the nodule interfaces and circularity of the nodule shape were calculated with an image-processing program, and the percentage of the nodule surrounded by emphysema was obtained. Statistical comparisons were made with a chi(2) or Fisher exact test and the Mann-Whitney U test. RESULTS: In patients with emphysema, there were no significant differences in fractal dimension, circularity, or frequency of lobulation or spiculation between malignant and benign nodules. Of the 41 nodules in patients with emphysema, 26 (63%) were correctly diagnosed. Thirteen benign nodules (65%) were diagnosed as malignant in patients with emphysema. Of the 40 nodules in nonemphysematous lungs, 37 (93%) were correctly diagnosed. The mean percentage of emphysema around the nodule was greater for misdiagnosed nodules than for correctly diagnosed nodules (P = .003). CONCLUSION: Malignant and benign nodules associated with emphysema exhibited considerably more overlap in CT features than did nodules in nonemphysematous lungs.

Aged↗

Complementary DNA expression array analysis suggests a lower expression of signal transduction proteins and receptors in cold and hot thyroid nodules.

Autonomously functioning thyroid nodules are characterized by an increased proliferation and function, which is predominantly caused by constitutively activating TSH receptor mutations leading to an activation of cAMP. In contrast to autonomously functioning thyroid nodules, cold thyroid nodules are functionally inactive and less differentiated. Their molecular cause is still unknown. To further investigate the pathophysiological aspects of autonomously functioning thyroid nodules and to elucidate the molecular etiology of cold thyroid nodules, it is essential to identify genes with differential expression in autonomously functioning thyroid nodules and cold thyroid nodules and to compare this expression to that in normal surrounding tissue. The list of possible candidates for differential regulation ranges from growth factors and their receptors to transcription factors or oncogenes. Therefore, we evaluated the potential of cDNA arrays and studied the expression of 588 known genes from 6 different classes of proteins in thyroid nodules characterized for their function. Forty-seven genes showed a differential expression between nodular and surrounding tissue identified by the expression arrays. The differential expression of 15 transcripts was verified by real-time PCR. About 25% of the transcripts determined by LightCycler PCR are considered false positives because data from PCR and array analysis did not agree. This indicates the reliability of cDNA expression arrays to identify differentially expressed genes in thyroid nodules compared with their surrounding tissue. The 15 selected genes were additionally quantified by real-time PCR in 7 additional cold thyroid nodules, autonomously functioning thyroid nodules, and their surrounding tissues. The highest number of differentially expressed genes was in the group of signal transduction proteins (4 of 38 detectable genes) and extracellular cell signaling and communication proteins (2 of 62 detectable genes). In contrast, transcripts of other classes of proteins were unchanged (e.g. DNA-binding molecules and stress responses). Most of the transcripts were down-regulated in autonomously functioning thyroid nodule and cold thyroid nodule compared with the respective surrounding tissue. This finding could be the result of a dominant activation of a signal transduction pathway, with the cAMP pathway being the likely candidate for autonomously functioning thyroid nodules. The qualitatively similar pattern of changes in this limited number of genes in autonomously functioning thyroid nodules and cold thyroid nodules could suggest a similar dominant activation of a specific signaling cascade in cold thyroid nodules as the constitutively activating mutations in autonomously functioning thyroid nodules.

Adult↗

The effect of pregnancy on thyroid nodule formation.

Epidemiology data have revealed a higher prevalence of nodular goiters in women than men in both iodine-sufficient and iodine-deficient areas. Increased prevalence of thyroid nodules has also been reported in women with higher gravidity. However, the association between pregnancy and thyroid nodule formation has never been studied. The aim of our study was to evaluate the incidence of thyroid nodules during pregnancy and determine whether pregnancy will induce thyroid nodule formation. Two hundred twenty-one healthy southern Chinese women in the first trimester of their pregnancy were studied prospectively. Thyroid ultrasonography, thyroid function tests, and urinary iodine excretion were measured at first, second, and third trimesters of pregnancy as well as 6 wk and 3 months postpartum. Thyroid nodules (>2 mm in any dimension on ultrasonography) were detected in 34 (15.3%) subjects at first trimester, with 12 (5.4%) subjects having more than one nodule. Eight subjects had clinically palpable nodules. Women with thyroid nodules were older (P < 0.01) and had higher gravidity (P < 0.02) than those women without thyroid nodules. The volume of the single/dominant nodules increased from 60 (14--344) mm(3), median (interquartile range) at first trimester to 65 (26-472) mm(3) at third trimester (P < 0.02). These nodules remained enlarged at 103 (25-461) mm(3) 6 wk postpartum (P < 0.005) and 73 (22-344) mm(3) at 3 months postpartum (P < 0.05). Patients with thyroid nodules had lower serum TSH values (P < 0.03) and higher Tg levels (P < 0.05) throughout pregnancy. Appearance of new nodules was detected in 25 (11.3%) women as pregnancy advanced so that by 3 months postpartum, the incidence of thyroid nodular disease was 24.4% (P < 0.02 vs. first trimester). Compared with those with no detectable nodules throughout pregnancy, subjects with new nodule formation had higher urinary iodine excretion from second trimester onward (P all < 0.05). However, no difference could be detected in their TSH and Tg levels throughout pregnancy. Fine-needle aspiration on nodules greater than 5 mm in any dimension after delivery (n = 21) confirmed the majority having histological features consistent with nodular hyperplasia. No thyroid malignancy was detected. In conclusion, pregnancy is associated with an increase in the size of preexisting thyroid nodules as well as new thyroid nodule formation. This may predispose to multinodular goiter in later life.

Adult↗

Detection of pulmonary nodules with helical CT: comparison of cine and film-based viewing.

OBJECTIVE: The purpose of our study was to determine whether cine viewing of helical CT scans of the chest improves the detection of pulmonary nodules in patients with known extrathoracic malignancy. SUBJECTS AND METHODS: Identical helical CT studies of the chest of 60 patients with known extrathoracic malignancy were reviewed for detection of pulmonary nodules. Four radiologists interpreted the helical CT studies. Pulmonary nodules were divided into four groups according to maximum diameter: group 1, nodules smaller than or equal to 5 mm; group 2, nodules larger than 5 mm but smaller than or equal to 10 mm; group 3, nodules larger than 10 mm but smaller than or equal to 20 mm; group 4, nodules larger than 20 mm. Interpreters also assigned a lesion conspicuity score of pulmonary nodules based on a four-point scale: one point for poor visibility, two points for adequate visibility, three points for good visibility, and four points for excellent visibility. Static film-based images printed on a laser printer were viewed on a light box. Cine viewing of helical CT scans from the same examinations was done on a commercially available workstation. The number, diameter, and conspicuity scores of pulmonary nodules detected at lung window settings were documented. RESULTS: Interpreters saw 266 nodules on cine viewing, whereas 237 nodules were seen with static film-based viewing. A significantly higher percentage of nodules that were smaller than or equal to 5 mm in diameter was found with cine viewing (n = 106) than with static film-based viewing (n = 81) (p < .05). Cine viewing (n = 105) also allowed a slightly but not significantly higher detection rate of nodules that were larger than 5 mm but smaller than or equal to 10 mm in diameter than did static film-based viewing (n = 101). We found no differences between cine (n = 55) and static film-based viewing (n = 55) in the detection of pulmonary nodules that were larger than 10 mm in diameter. The mean conspicuity score of nodules was significantly higher with cine viewing (2.9 +/- 0.2) than with film-based viewing (2.4 +/- 0.2) (p < .05). CONCLUSION: Cine viewing of helical CT scans significantly increases the detection rate of pulmonary nodules that are smaller than or equal to 5 mm in diameter. However, we found no significant difference between cine and film-based viewing in the detection rate of pulmonary nodules that were larger than 5 mm in diameter. The advantages of cine viewing may be attributed to both the larger image size and the ability to scroll through images for improved differentiation between vessels and nodules.

Female↗

Volumetric measurements of lung nodules with multi-detector row CT: effect of changes in lung volume.

OBJECTIVE: To evaluate how changes in lung volume affect volumetric measurements of lung nodules using a multi-detector row CT. MATERIALS AND METHODS: Ten subjects with asthma or chronic bronchitis who had one or more lung nodules were included. For each subject, two sets of CT images were obtained at inspiration and at expiration. A total of 33 nodules (23 nodules > or =3 mm) were identified and their volume measured using a semiautomatic volume measurement program. Differences between nodule volume on inspiration and expiration were compared using the paired t-test. Percent differences, between on inspiration and expiration, in nodule attenuation, total lung volume, whole lung attenuation, and regional lung attenuation, were computed and compared with percent difference in nodule volume determined by linear correlation analysis. RESULTS: The difference in nodule volume observed between inspiration and expiration was significant (p < 0.01); the mean percent difference in lung nodule volume was 23.1% for all nodules and for nodules > or =3 mm. The volume of nodules was measured to be larger on expiration CT than on inspiration CT (28 out of 33 nodules; 19 out of 23 nodules > or =3 mm). A statistically significant correlation was found between the percent difference of lung nodule volume and lung volume or regional lung attenuation (p < 0.05) for nodules > or =3 mm. CONCLUSION: Volumetric measurements of pulmonary nodules were significantly affected by changes in lung volume. The variability in this respiration-related measurement should be considered to determine whether growth has occurred in a lung nodule.

Adult↗

Effect of blood vessels on measurement of nodule volume in a chest phantom.

PURPOSE: To identify, by using a chest phantom, whether vessels that contact lung nodules measuring less than 5 mm in diameter will affect nodule volume assessment. MATERIALS AND METHODS: Forty synthetic nodules (20 with ground-glass attenuation and 20 with solid attenuation) that measured less than 5 mm in diameter were placed into a chest phantom either adjacent to (n = 30) or isolated from (n = 10) synthetic vessels. Nodules were imaged by using low-dose (20 mAs) and diagnostic (120 mAs) multi-detector row computed tomography (CT). Nodules that were known to lie in direct contact with vessels were confirmed by visual inspection. Nontargeted 1.25 x 1.00-mm sections were analyzed with a three-dimensional computer-assisted method for measuring nodule volume. A mixed-model analysis of variance was used to examine the influence of several factors (eg, the presence of adjacent vessels; tube current-time product; and nodule attenuation, diameter, and location) on measurement error. RESULTS: The mean absolute error (MAE) for all nodules adjacent to vessels was 2.3 mm(3), which was higher than the MAE for isolated nodules (1.9 mm(3)) (P < .001). This difference proved significant only for diagnostic CT (2.2 mm(3) for nodules adjacent to vessels vs 1.3 mm(3) for nodules isolated from vessels) (P < .05). A larger MAE was noted for nodules with ground-glass attenuation (2.3 mm(3)) versus those with solid attenuation (2.0 mm(3)), for increasing nodule volume (1.66 mm(3) for nodules smaller than 20 mm(3) vs 2.83 mm(3) for nodules larger than 40 mm(3)), and for posterior nodule location (P < .05). CONCLUSION: The presence of a vessel led to a small yet significant increase in volume error on diagnostic-quality images. This represents less than one-third of the overall error, even for nodules larger than 40 mm(3) or approximately 4 mm in diameter. This increase, however, may be more important for smaller nodules with errors of less than 3 mm(3).

Diagnostic Errors↗

Outcome of long standing solitary thyroid nodules.

We investigated the outcome of long standing palpable solitary thyroid nodules by surveying 441 patients and examining 140 patients who had untreated thyroid nodules for 15 +/- 4.5 years. In our clinical survey, the most common outcome was disappearance of the thyroid nodule (38.3%). Also a significant number of patients (36.3%) underwent surgery in other hospitals. Five (1.1%) patients died of thyroid cancer. When thyroid nodules were re-examined, most nodules indeed decreased in size or disappeared; however, 13% of nodules increased in size. Ultrasound of the nodules showed that most solitary nodules were multiple and partially cystic and solid. There was an increased incidence of calcification in long standing nodules. Thyroid cancer was found by fine needle aspiration biopsy in 26.3% of enlarging nodules and 6.4% of nodules without changing size. The risk of cancer decreased when the size of the nodule decreased. A total of 15 patients with suspicion of malignancy underwent surgery. Surgical procedures were lobectomy, near total thyroidectomy, or resection of nodules with or without modified neck dissection. Seven patients had papillary carcinoma and 2 patients with benign cytology had microscopically evident papillary carcinoma. In our study, the majority of palpable solitary thyroid nodules tended to decrease in size; these nodules do not require treatment. Enlarging solid nodules are a definite risk for thyroid cancer. If the size of the nodule remains the same, judicious approach with fine needle aspiration biopsy is needed.

Adult↗

Aspiration needle biopsy in preoperative selection of thyroid nodules defined at fine-needle aspiration as microfollicular lesions.

The palpable thyroid nodules that are diagnosed as microfollicular by fine-needle aspiration cytologic analysis are usually excised for the low probability that the nodule is a well-differentiated follicular cancer. The authors retrospectively assess the use of aspiration needle biopsy (either 16- or 18-gauge needles) in the preoperative selection of the nodules diagnosed as microfollicular at fine-needle aspiration (either 20- or 22-gauge needles). Aspiration needle biopsy is a type of large needle biopsy that is a relatively easy and innocuous method of obtaining tissue fragments for preoperative histologic examination of palpable thyroid nodules. From 1980 through 1996, 6,314 patients with palpable thyroid nodules were examined by fine-needle aspiration; 29.5% of these nodules were also examined preoperatively by aspiration needle biopsy. Of all the patients with nodules, 6% received a fine-needle aspiration diagnosis of microfollicular nodule. Two hundred sixty of the 380 nodules (68%) that were diagnosed as microfollicular at fine-needle aspiration were also examined by aspiration needle biopsy; inadequate specimens were obtained in 17% of cases; pure microfollicular structure was confirmed by aspiration needle biopsy in 35% of the nodules; and aspiration needle biopsy showed the remaining 48% to contain a macrofollicular component suggesting a benign hyperplastic lesion. Seventeen nodules that were found to be microfollicular at fine-needle aspiration cytologic analysis and micromacrofollicular at aspiration needle biopsy were excised and the postoperative result was benign in all cases. Twenty-five nodules diagnosed as microfollicular either on both fine-needle aspiration and aspiration needle biopsy were excised and the postoperative diagnoses were benign (20 nodules) or malignant (5 nodules). These data indicate that aspiration needle biopsy can be used for preoperative selection of the nodules that are microfollicular at fine-needle aspiration by identifying the nodules with high probability of being malignant and thus contributing to the reduction in the number of surgical operations for benign nodules.

Adenocarcinoma, Follicular↗

Small nodules detected on chest radiography: does size predict calcification?

STUDY OBJECTIVES: To determine whether the likelihood of lung nodule calcification can be predicted from nodule size as measured on a chest radiograph (CXR). DESIGN: Retrospective review of CXRs of patients with lung nodules < or =1 cm in size detected on CT scanning. CT images were used to identify calcifications and to provide spatial localization for readers to visualize nodules on a CXR and to measure their size. A subset of these nodules then was reexamined by different readers who did not view the CT scans SETTING: Two university hospitals (Albuquerque, NM; Dallas, TX) and a US Air Force/Veterans Administration medical center (Albuquerque, NM). PATIENTS: Two hundred thirty-six nodules in 185 patients RESULTS: One half of the nodules (118) seen on CT scans could not be located on CXR, of which 8 (7%) were calcified. The prevalence of calcifications in the other 118 nodules visualized on CXRs was much higher (71 of 118 nodules [60%]; p<0.005). Among the nodules visualized on CXRs, those < 7 mm in diameter (44 of 57 nodules [77%]) were more likely to be calcified than those > or = 7 mm in diameter (27 of 61 nodules [44%]; p<0.005). Radiographs of 42 of the smallest nodules visualized on CXRs by the initial readers later were examined prospectively by different readers who did not have access to the CT images. Thirty of 33 of the calcified nodules (91%) but only 3 of 9 of the noncalcified nodules (33%) were detected (p<0.005). These readers also recorded 40 additional small nodules that were not seen on CT scans, which were considered to be false-positives. CONCLUSIONS: Nodules detected on CXRs that measure <7 mm in size are likely to be calcified or to represent a false-positive finding.

Calcinosis↗

Is fine-needle aspiration (FNA) of multiple thyroid nodules justified?

BACKGROUND: The clinical management of patients with solitary thyroid nodule is well established; however, the evaluation of patients with multiple thyroid nodules is controversial. The aim of this study was to assess if there is a correlation between the risk of malignancy and number of thyroid nodules. DESIGN: The study cohort included 2,884 patients (2,410 females and 474 males) with 3,274 thyroid nodules that underwent FNA under ultrasound guidance between November 1997 and April 2004. Multiple thyroid nodules were aspirated in 360 patients; 2 in 332 (291 females, 41 males), 3 nodules in 26 (23 females, 3 males), and 4 nodules in 2 patients (1 female, 1 male). Subsequent information regarding the histological diagnosis was obtained in the cases that underwent surgical excision. RESULTS: The average age for patients with single or multiple nodules was the same (51 yr). The FNA specimens were diagnosed as benign (n = 1,663, 51%), neoplasm (n = 880, 27%), suspicious for neoplasm or papillary carcinoma (n = 234, 7%), malignant (n = 187, 6%), and non-diagnostic (n = 310, 9%). Surgical excision was performed in 1,135 patients: 993 patients with single nodules and 142 patients with multiple nodules. The surgical pathology diagnosis was benign in 656 nodules (52%) and malignant in 596 nodules (48%). In the malignant category 153 tumors were papillary microcarcinoma (<1 cm). Excluding these cases, the malignancy rate was 39% in patients with single nodules, 41% with two nodules, and 21% with three nodules. CONCLUSIONS: The cancer risk is similar for patients with one or two nodules over 1 cm and decreases with three or more thyroid nodules.

Biopsy, Fine-Needle↗