New Approach For Early Detection Research Articles

Machine learning for prediction of incident heart failure and heart failure hospitalisation: multi-cohort development, validation and association with clinical phenotypes

Abstract Background Delayed heart failure (HF) diagnosis is associated with adverse outcomes and costs of hospitalisation.(1,2) Whilst previous tools have been developed to predict incident HF,(3) risk of HF incidence may correlate poorly with risk of HF hospitalisation, which may be more important in targeting diagnostics. Purpose To develop and validate a novel decision support tool for prediction of incident HF and HF hospitalisation, and investigate association of score with HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Methods We developed the models (FIND-HF) in UK primary care health record data from individuals aged ≥40 years without known HF (Jan 2, 1998 to Feb 28, 2022), randomly divided into training (80%) and testing (20%) datasets. We evaluated logistic regression and supervised machine learning models for prediction of 1- and 5- year HF and HF hospitalisation risk in the testing dataset with internal bootstrap validation. Models were externally validated for HF hospitalisation in data from a Taiwanese university hospital. Association of FIND-HF score with HF phenotypes of HFpEF and HFrEF was assessed in two prospective cohorts, the MATCH registry of patients diagnosed with HFrEF and the FIND-AF cohort of individuals at higher predicted risk of atrial fibrillation who underwent echocardiography. Results Of 565 284 UK individuals (mean age 68.9 (SD 12.2) years, 49.2% women), incidence of HF and HF hospitalisation was 1.1% and 0.5% at 1-year, and 6.6% and 3.4% at 5-years, respectively. Prediction performance was superior for machine learning algorithms compared with logistic regression, with best performance for XGBoost (area under receiver operating characteristic curve (AUROC) at 1 and 5-years: 0.755 and 0.723 for incident HF, and 0.738 and 0.711 for incident HF hospitalization). On external validation in 106,026 individuals in Taiwan (mean age 64.7 (SD 10.6) years, 52.8 % women), HF hospitalisation incidence was 0.71%, and 2.46% at 1- and 5- years, respectively, and discrimination performance was excellent (AUROC at 1- and 5-years: 0.834 and 0.843). When the FIND-HF score was applied to individuals in the MATCH cohort (n = 133, mean age 69.0 (SD 11.7) years, 38.3% women) and FIND-AF cohort (n = 82, mean age 71.6 (SD 7.5) years, 50.0% women), the distribution of score to clinical phenotypes demonstrated a binomial distribution (Figure 1), and likelihood of HFpEF diagnosis correlated with the numeric score (Figure 2). Conclusions The machine learning FIND-HF decision support tool can accurately identify individuals at risk of incident HF and HF hospitalisation, to enable new approaches for early detection and prevention. The variation of score amongst high risk individuals with different HF clinical phenotypes emphasizes the distinct pathophysiological pathways but shared adverse outcome profile across the HF syndrome.Figure 1Figure 2

MA08.11 Incidental Lung Nodule Program: A New Approach for Early Detection and Management of Lung Cancer

MA08.11 Incidental Lung Nodule Program: A New Approach for Early Detection and Management of Lung Cancer

EEG biomarkers analysis in different cognitive impairment after stroke: an exploration study.

Stroke is a cerebrovascular illness that brings about the demise of brain tissue. It is the third most prevalent cause of mortality worldwide and a significant contributor to physical impairment. Generally, stroke is triggered by blood clots obstructing the brain's blood vessels, or when these vessels rupture. And, the cognitive impairment's evaluation and detection after stroke is crucial research issue and significant project. Thus, the objective of this work is to explore an potential neuroimage tool and find their EEG biomarkers to evaluate and detect four cognitive impairment levels after stroke. In this study, power density spectrum (PSD), functional connectivity map, and one-way ANOVA methods were proposed to analyze the EEG biomarker differences, and the number of patient participants were thirty-two human including eight healthy control, mild, moderate, severe cognitive impairment levels, respectively. Finally, healthy control has significant PSD differences compared to mid, moderate and server cognitive impairment groups. And, the theta and alpha bands of severe cognitive impairment groups have presented consistent superior PSD power at the right frontal cortex, and the theta and beta bands of mild, moderated cognitive impairment (MoCI) groups have shown significant similar superior PSD power tendency at the parietal cortex. The significant gamma PSD power difference has presented at the left-frontal cortex in the mild cognitive impairment (MCI) groups, and severe cognitive impairment (SeCI) group has shown the significant PSD power at the gamma band of parietal cortex. At the point of functional connectivity map, the SeCI group appears to have stronger functional connectivity compared to the other groups. In conclusion, EEG biomarkers can be applied to classify different cognitive impairment groups after stroke. These findings provide a new approach for early detection and diagnosis of cognitive impairment after stroke and also for the development of new treatment options.

Evaluation of chondrocyte dedifferentiation mechanisms using confocal Raman microscopy

Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.

Probes for cancer metastasis imaging and therapeutic targeting

Progression to metastases remains the overriding cause of cancer-associated mortality. Metastatic cancer is not amenable to surgery and its treatment is further complicated by the development of therapy resistance often observed at advanced cancer stages. Early detection of metastases is therefore critical but has been limited by the lack of probes that can effectively localize them. Similar challenges persist with therapeutics specifically targeting metastasized cancer cells. Thus, agents that specifically target disseminating tumor cells at an early stage could produce new theranostic applications and be transformative for the survival of patients with advanced cancers. Recent studies have described new approaches for early detection and targeted eradication of metastatic cancer. Here we summarize the results from preclinical validation of the experimental probes reported to date.

Exploring Microbial Dysbiosis in Orchards Affected by Little Cherry Disease

The phytoplasma ‘ Candidatus Phytoplasma pruni’, a causative agent of little cherry disease (LCD), has become an increasing problem for sweet cherry growers in Washington State, which is the largest producer of cherry fruit in the United States. The control of LCD currently relies on the identification and removal of infected trees, which has proven to be difficult because of the prolonged asymptomatic but still contagious state of the disease, and the lack of reliable and economical tests. Thus, the development of new approaches for early detection of LCD will be an important step in the successful control of this tree fruit disease. To identify potential microbial indicators of ‘ Ca. P. pruni’ infection, we evaluated the bacterial and fungal communities in the roots of cherry trees from two different orchards that were (i) infected with ‘ Ca. P. pruni’ and symptomatic; (ii) infected with ‘ Ca. P. pruni’ but remained asymptomatic; and (iii) healthy, with non-‘ Ca. P. pruni’-infected trees. We found significant variation in the microbiomes between the two cherry orchards, with the location being a stronger driving factor determining the fungal compared with the bacterial community. The fungal communities were less affected by the disease conditions compared with the bacterial microbiome. Overall, this study demonstrates the feasibility of the microbiome approach for the early detection of LCD caused by ‘ Ca. P. pruni’ but also demonstrates that more orchards need to be sampled because location was a stronger contributor to the microbiome of cherry tree roots than disease condition.

OncoUroMiR: Circulating miRNAs for Detection and Discrimination of the Main Urological Cancers Using a ddPCR-Based Approach.

The three most common genitourinary malignancies (prostate/kidney/bladder cancers) constitute a substantial proportion of all cancer cases, mainly in the elderly population. Early detection is key to maximizing the patients' survival, but the lack of highly accurate biomarkers that might be used through non-/minimally invasive methods has impaired progress in this domain. Herein, we sought to develop a minimally invasive test to detect and discriminate among those urological cancers based on miRNAs assessment through ddPCR. Plasma samples from 268 patients with renal cell (RCC; n = 119), bladder (BlCa; n = 73), and prostate (PCa; n = 76) carcinomas (UroCancer group), and 74 healthy donors were selected. Hsa-miR-126-3p, hsa-miR-141-3p, hsa-miR-153-5p, hsa-miR-155-5p, hsa-miR-182-5p, hsa-miR-205-5p, and hsa-miR-375-3p levels were assessed. UroCancer cases displayed significantly different circulating hsa-miR-182-5p/hsa-miR-375-3p levels compared to healthy donors. Importantly, the hsa-miR-155-5p/hsa-miR-375-3p panel detected RCC with a high specificity (80.54%) and accuracy (66.04%). Furthermore, the hsa-miR-126-3p/hsa-miR-375-3p panel identified BlCa with a 94.87% specificity and 76.45% NPV whereas higher hsa-miR-126-3p levels were found in PCa patients. We concluded that plasma-derived miRNAs can identify and discriminate among the main genitourinary cancers, with high analytical performance. Although validation in a larger cohort is mandatory, these findings demonstrate that circulating miRNA assessment by ddPCR might provide a new approach for early detection and risk stratification of the most common urological cancers.

Hounsfield units on abdominal computed tomography: a new tool for predicting osteoporosis.

Osteoporosis can cause bone fractures and disability, but early diagnosis faces challenges. Our proposed diagnostic indicators offer a new approach for early detection, which benefits early identification. To determine the most appropriate threshold for predicting osteoporosis in patients with each section of vertebral body. A retrospective analysis of 210 patients, including 646 vertebrae, who had both abdominal computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) within six months. The correlation between DXA T-score and CT Hounsfield units (HU) values was tested by Pearson. The area under the curve (AUC) was calculated using the threshold obtained from the regression equation. The thresholds matching the T-score of -2.5 were 85, 95, 85, and 90 HU for the upper axial plane of the vertebral body (Lau), the middle axial plane of the vertebral body (Lam), the lower axial plane of the vertebral body (Lad), and the mid-sagittal plane of the vertebral body (Lsm), respectively. Defining osteoporosis using CT as Lau ≤ 85, Lam ≤ 95, Lad ≤ 85, or Lsm ≤ 90 HU had a specificity of 88.1% (116/134) and sensitivity of 90.8% (69/76) for distinguishing DXA osteoporosis of the lumbar spine in 210 patients. T-score ≤-2.5 defined as Lau ≤85 or Lam ≤95 or Lad ≤85 or Lsm ≤90 HU had a specificity of 85.9% (275/320) and sensitivity of 82.8% (270/326) for DXA T-score ≤-2.5 in 646 lumbar vertebrae. CT HU values obtained based on different sections of the vertebral body in abdominal CT can be used as a supplementary measure to assess osteoporosis.

Visualization of endoplasmic reticulum viscosity in the liver of mice with nonalcoholic fatty liver disease by a near-infrared fluorescence probe

Nonalcoholic fatty liver disease (NAFLD) can cause serious liver damage. Early diagnosis and effective treatment of NAFLD can greatly improve treatment rates. The initiation and development of NAFLD has been closely linked to endoplasmic reticulum (ER) stress, which might cause ER viscosity variations. Therefore, if the internal relationship between ER viscosity and NAFLD is clarified, an effective approach for early diagnosis may result. Herein, we fabricated a novel near-infrared (NIR) fluorescence imaging probe, Er-V, for monitoring ER viscosity through a molecular rotor strategy. Er-V exhibited a strong NIR fluorescence signal (at 626 nm) when the environmental viscosity hindered the rotation of the malononitrile group. Using Er-V, we successfully observed a significant enhancement in viscosity in the liver of mice with NAFLD. Therefore, this imaging method based on Er-V is expected to provide a new approach for early detection and diagnosis of NAFLD.

N-Glycoproteins Have a Major Role in MGL Binding to Colorectal Cancer Cell Lines: Associations with Overall Proteome Diversity.

Colorectal cancer (CRC) is the second-leading cause of cancer death worldwide due in part to a high proportion of patients diagnosed at advanced stages of the disease. For this reason, many efforts have been made towards new approaches for early detection and prognosis. Cancer-associated aberrant glycosylation, especially the Tn and STn antigens, can be detected using the macrophage galactose-type C-type lectin (MGL/CLEC10A/CD301), which has been shown to be a promising tool for CRC prognosis. We had recently identified the major MGL-binding glycoproteins in two high-MGL-binding CRC cells lines, HCT116 and HT29. However, we failed to detect the presence of O-linked Tn and STn glycans on most CRC glycoproteins recognized by MGL. We therefore investigated here the impact of N-linked and O-linked glycans carried by these proteins for the binding to MGL. In addition, we performed quantitative proteomics to study the major differences in proteins involved in glycosylation in these cells. Our results showed that N-glycans have a significant, previously underestimated, importance in MGL binding to CRC cell lines. Finally, we highlighted both common and cell-specific processes associated with a high-MGL-binding phenotype, such as differential levels of enzymes involved in protein glycosylation, and a transcriptional factor (CDX-2) involved in their regulation.

Bacteria-Instructed In Situ Aggregation of AuNPs with Enhanced Photoacoustic Signal for Bacterial Infection Bioimaging.

The emergence of drug-resistant bacteria is becoming the focus of global public health. Early-stage pathogen bioimaging will offer a unique perspective to obtain infection information in patients. A photoacoustic (PA) contrast agent based on functional peptide modified gold nanoparticles (AuNPs@P1) is developed. These nanoparticles can be specifically tailored surface peptides by bacterial overexpressed enzyme inducing in situ aggregation of the gold nanoparticles. In the meantime, the close aggregation based on the hydrogen bonding, π-π stacking, and hydrophobic interaction of the peptide residues on the surface of gold nanoparticles exhibits a typical redshifted and broadened plasmon band. In addition, this active targeting and following in situ stimuli-induced aggregation contribute to increased nanoparticle accumulation in the infected site. Finally, the dynamic aggregation of AuNPs@P1 results in dramatically enhanced photoacoustic signals for bioimaging bacterial infection in vivo with high sensitivity and specificity. It is envisioned that this PA contrast agent may provide a new approach for early detection of bacterial infection in vivo.

Breast abnormality based early diagnosis of breast cancer using non-invasive digital infrared thermal imaging

Breast cancer is one of the most leading and common cause of cancer. It can be detected by infrared thermal imaging Technique by observing the temperature distribution on the breast. Breast thermography is considered as a valuable tool for early breast tumours detection. The fast growing tumour has a higher metabolic rate and associated increase in local vascularisation. It will cause the occurrence of some asymmetric heat patterns. Clinical interpretation of a breast thermogram can be done on the asymmetry analysis of the heat patterns visually and subjectively. In this paper, a new approach for early detection of breast cancer is proposed using asymmetry analysis of breast thermograms. The heat patterns are segmented and the asymmetry analysis is performed by using histogram generation and feature extraction. Extracted statical features clearly indicate the abnormality of a breast thermogram.

Breast abnormality based early diagnosis of breast cancer using non-invasive digital infrared thermal imaging

Breast cancer is one of the most leading and common cause of cancer. It can be detected by infrared thermal imaging Technique by observing the temperature distribution on the breast. Breast thermography is considered as a valuable tool for early breast tumours detection. The fast growing tumour has a higher metabolic rate and associated increase in local vascularisation. It will cause the occurrence of some asymmetric heat patterns. Clinical interpretation of a breast thermogram can be done on the asymmetry analysis of the heat patterns visually and subjectively. In this paper, a new approach for early detection of breast cancer is proposed using asymmetry analysis of breast thermograms. The heat patterns are segmented and the asymmetry analysis is performed by using histogram generation and feature extraction. Extracted statical features clearly indicate the abnormality of a breast thermogram.

Abstract IA13: A practical approach to reducing the burden of ovarian cancers

Abstract Ovarian cancer has seen a modest improvement in five-year survival over the past three decades. It is well known that the lack of further success is solely due to the advanced stage at diagnosis for most women with ovarian cancers. To reduce the burden of ovarian cancer, we must decrease the incidence (primary prevention), improve early detection (secondary prevention), or develop more effective treatments for newly diagnosed disease (tertiary prevention). Large scale screening trials using traditional methods of imaging and tumor markers have not led to meaningfully stage migration, reduction in mortality, or widespread clinical adoption. In fact, the FDA recently issued a safety alert about the risks associated with the use of tests being marketed as ovarian cancer screening tests. The FDA was specifically concerned about ovarian cancer screening tests being used in lieu of established risk-reduction approaches. This presentation will review practical approaches to reducing the burden of ovarian cancer through primary, secondary, and tertiary prevention. Genetic testing of probands for BRCA1 and BRCA2 germline mutations alone and cascade testing of relatives are currently available approaches to reduce the incidence of ovarian cancer by more than 10%. This tactic is consistent with professional guidelines and has the added advantage of identifying therapeutic options for ovarian cancer patients that could contribute to tertiary prevention efforts today and in the future. Lower penetrant genes also have the potential to lead to primary prevention through risk reduction strategies, but further data is required to firmly establish appropriate age-based recommendations. The identification of the distal fallopian tube as a likely site of origin for most ovarian cancers has opened a new domain for ovarian cancer primary prevention. Some governmental organizations suggest population-based bilateral salpingectomy at the time of any pelvic or abdominal surgery for primary prevention of ovarian cancers considering that one-third of US women will have a hysterectomy by age 70. The reasons for success and failure of this approach will be discussed. The fallopian tube as the site of origin for ovarian cancers has led to new approaches for early detection. The anatomy of the fallopian tube and its proximity to the lower genital tract has led to the development of creative strategies for sampling derivatives of precursor lesions and early invasive disease. Collection of uterine fluid for proteomic analyses and DNA sequencing holds promise for enrichment of cancer-specific biomolecules. Cervical pap smears and the collection of vaginal secretions offer a less invasive approach to early detection through similar theoretical avenues. Through the study of long-term survivors of advanced stage high-grade serous ovarian cancer, we have learned that primary surgical cytoreduction reduces the risk of cancer recurrence and serves as a useful approach to tertiary prevention. Citation Format: Douglas A. A practical approach to reducing the burden of ovarian cancers. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA13.

A positive feedback loop between STAT3 and cyclooxygenase‐2 gene may contribute to Helicobacter pylori‐associated human gastric tumorigenesis

Persistent infection with Helicobacter pylori (H. pylori) contributes to gastric diseases including chronic gastritis and gastric cancer. However, the pathogenesis of this carcinogenic bacterium has not been completely elucidated. Here, we report that H. pylori rapidly triggers STAT3 signaling and induces STAT3-dependent COX-2 expression both in vitro and in vivo. STAT3 upregulates COX-2 by binding to and increasing the activity of COX-2 promoter. COX-2 in turn regulates IL-6/STAT3 signaling under basal conditions and during H. pylori infection. These findings suggest that a positive feedback loop between STAT3 and COX-2 exists in the basal condition and H. pylori infectious condition. Immunohistochemical staining revealed that H. pylori-positive gastritis tissues exhibited markedly higher levels of pSTAT3(Tyr705) than H. pylori-negative ones. High pSTAT3(Tyr705) levels are correlated with intestinal metaplasia and dysplasia, suggesting pSTAT3(Tyr705) may be useful in the early detection of gastric tumorigenesis. Additionally, a strong positive correlation between STAT3/pSTAT3(Tyr705) levels and COX-2 expression was identified in gastritis and gastric cancer tissues. Together, these findings provide new evidence for a positive feedback loop between STAT3 signaling and COX-2 in H. pylori pathogenesis and may lead to new approaches for early detection and effective therapy of gastric cancer

Use of a new generation of capillary electrophoresis to quantify circulating free DNA in non-small cell lung cancer

Circulating free DNA (cfDNA) is present in higher concentration in non-small-cell lung cancer (NSCLC) patients than in controls. This study was designed to assess the sensitivity and specificity of Agilent 2100 Bioanalyzer to identify patients with NSCLC and to compare it with quantitative RealTime-PCR (RT-qPCR) assay. 30 NSCLC patients and 26 controls were analyzed. The amount of cfDNA was determined both through quantitative RT-PCR targeting the human β-actin gene and by Agilent 2100 Bioanalyzer. Performances of the assays were calculated by the receiver operating characteristic (ROC) curves. The mean cfDNA concentration, obtained through the use of Agilent 2100 Bioanalyzer, in NSCLC patients (94.5ng/mL) was almost twice the concentration detected in controls (42.8ng/mL) as well as found by RT-qPCR (22.5ng/mL vs 7.1ng/mL, p<0.001). The area under curve of Agilent 2100 Bioanalyzer and RT-PCR showed that there are no statistically significant differences between these tests (p<0.92).This study shows that Agilent 2100 Bioanalyzer is an effective diagnostic tool to discriminate NSCLC patients from healthy individuals and suggests a new approach for early detection of NSCLC.

Experience of the health promotion clinics in Aseer region, Saudi Arabia.

Context:Health promotion is the most important element of primary health care. Therefore, it is essential for the health team to apply such activity.Objective:To describe a newly established health promotion clinic at primary health care centers, in Abha city, KSA.Materials and Methods:The study was conducted during the year 2009. The files of 429 individuals were reviewed after one year from attending the health promotion clinics in Abha city, KSA. Master sheet was designed based on the relevant items of the file. The health promotion services used in the study were based on the recommendation of the relevant guidelines. Data entry and analysis was carried out using Statistical Program for the Social Sciences (SPSS). P-values less than 0.05 were selected for statistical significance.Results:After one year, the percentage of the individuals who intake imbalanced diet and did not perform any type of physical activity was more than 90% while 8% are currently smokers and 14% had depression. Clinical examination and investigation revealed that more than one quarter of our subjects were overweight. Obesity was 42% in males versus 51% in females (P<0.04). Pre-hypertension and hypertension were detected among 44 and 12% respectively. About one fifth of our subjects had pre-diabetes 21% and 3% were confirmed to have diabetes mellitus. Diet and physical activity counseling was given to all participants while referral to concerned clinics was done for individuals who suffer from high blood sugar, abnormal lipid profile, obesity and depression.Conclusion:This study demonstrated that health promotion clinics provided by trained professional health care team can be used as a new approach for early detection and management of the common health problems in primary health care centers.

Corrections: 2009 San Antonio Breast Cancer Symposium Abstracts

Corrections: 2009 San Antonio Breast Cancer Symposium Abstracts

New Approach for Early Detection of Breast Cancer in Iran.

Abstract Introduction:Approximately 50% of newly diagnosed breast cancers occur in developing countries and it is the most common cancer amongst women in these countries. Majority of patients seek medical help late and in an advanced stage of the disease and there is a lack of national screening program. Moreover, some of these countries suffer from lack of diagnostic and treatment facilities to deal with their symptomatic patients. It seems, therefore, that the pressing need is detection of palpable breast cancer at an early stage.Increasing women's breast cancer awareness by mass education is not only the key to achieve this goal, but it is the basic pre-requisite for implementing the mass screening for breast cancer. Electronic media such as TV programs and Short Message Service (SMS) are easily accessible and relatively cheap in majority of these countries.This study which was designed in Iran and looked at population within one province in this country, aims to study whether the use of electronic media leads to increase patients' awareness and change in their behavior by early presentation and therefore smaller breast tumour on diagnosis and as a result increase in survival.Methods:Semnan province (in the north east of Iran with 588180 populations) was selected as the interventional group and two neighborhood regions with similar population were selected as controls. At first, the knowledge, attitude and practice of women and health care providers during the past year were assessed as a baseline. All public and private health providers were re-educated for breast cancer early detection. The intervention was entitled 'Breast Month', three Breast Month's campaign during two years were planned. In each Breast month, eight 30 minutes TV programs were designed and broadcasted by local TV network and two SMS with short message on breast cancer awareness were sent to 170 000 customers (1.3 lines for each family). The study endpoints include the feasibility of using electronic media for breast cancer awareness and change in knowledge, attitude, and practice of women; breast tumor registration; patients' quality of life and their survival rate in both the case and control groups.Results:The women's knowledge about breast cancer was 67.86% and 71.08% of women had positive attitude to breast cancer early detection. During the control period, the average number of breast self examination (BSE) per woman was 4.68; but 47.6%have not done any BSE by themselves, and 79.50% did not referr to the physician for breast clinical examination and only 8.50% had undergone mammography. During the past year 42 new cases of breast cancer were diagnosed (14.67/105 crude incidence rate and 19.81/105 Age specified Incidence Rate).Conclusions:This study in its first phase has showed It is feasible to use electronic media and sms service in low to middle income countries for breast cancer awareness despite some cultural restrictions. Also there are low baseline level of BSE and very low baseline level of clinical eaxamination and mammography by Iranian women. Increased awareness has resulted in increase detection of breast cancer and the second phase is studying the effect on down staging as a result of increased awareness. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6074.

In vivo detection of iron and neuromelanin by transcranial sonography – a new approach for early detection of substantia nigra damage

In more than 90% of patients with idiopathic Parkinson's disease (PD) hyperechogenicity of the substantia nigra (SN) can be found by transcranial sonography (TCS) as a typical, stable sign. Animal experiments provided first evidence that SN hyperechogenicity may be associated with increased tissue iron levels. Two consecutive studies revealed the same association in human brain. Postmortem brains of 60 subjects without clinical signs for Parkinson's disease during life time at different ages were scanned by ultrasound with planimetric measurement of the echogenic area of the SN. Afterwards the SN was dissected and used for histological examination and determination of iron content in all brains as well as ferritin and neuromelanin content in 40 brains. A significant positive correlation was found between the echogenic area of the SN and the concentration of iron, H- and L-ferritins. A multivariate analysis performed considering the iron content showed a significant negative correlation between echogenicity and neuromelanin content of the SN. Iron staining confirmed the biochemical findings. In PD a typical loss of neuromelanin and increase of iron is observed in this brain area. However, it is not clear yet, whether iron accumulation is a primary cause or a secondary phenomenon in the disease process. Screening of genes involved in brain iron metabolism showed a significant association of some sequence variations of the ceruloplasmin gene with PD. Others were associated with the ultrasound marker for increased iron levels in both PD patients and control subjects. As SN hyperechogenicity is typical for PD or subjects with a preclinical impairment of the nigrostriatal system, these findings indicate that TCS enables the detection of increased iron and decreased neuromelanin levels at the SN, even before the clinical manifestation of PD.