Identification Of Tumor Type Research Articles

Breast cancer brain metastases show increased levels of genomic aberration-based homologous recombination deficiency scores relative to their corresponding primary tumors

BackgroundBased on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor. Patients and methodsWe used a previously published next generation sequencing dataset of 21 matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also carried out the myChoice HRD analysis on an independent cohort of 17 breast cancer patients with matched primary/brain metastasis pairs. ResultsAll of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort, the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria. ConclusionsThe consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.

Treatment patterns of children with spine and spinal cord tumors: national outcomes and review of the literature.

Tumors of the spine in children are rare, and further clinical description is necessary. This study investigated epidemiology, interventions, and outcomes of pediatric patients with spine and spinal cord tumors. The National Inpatient Sample and Kids' Inpatient Database were used for the study. Outcomes were studied, and bivariate significant trends were analyzed in a multivariate setting. Analysis of 2870 patients between 2000 and 2009 found a median age of diagnosis of 11years (Tables 1 and 2). Most were white (65.2%) and had private insurance (62.3%), and 46.8% of procedures were emergent operations. Treatment occurred at teaching (93.6%) and non-children's hospitals (81.1%). Overall mortality rate was 1.7%, non-routine discharges occurred at a rate 19.9%, complications at 21.1%, and average total charges were $66,087. A majority of patients (87.5%) had no intervention, and of those patients receiving treatment, 78.2% underwent surgery and 23.1% had radiotherapy. Treatment with surgery alone increased significantly over time (p<0.0001). Odds ratio (OR) of mortality was significantly higher in 2006 (OR 3.5) and 2009 (OR 2.6) when compared to 2000. Complications (OR 7.9) and disease comorbidities (OR 1.5) were associated with significantly increased odds of mortality. Hospital characteristics, length of stay, and charges remained relatively unchanged. In recent years, there has been a decreasing incidence of spine and spinal cord tumors in children. Notably, a higher mortality rate is evident over time in addition to an increase in the proportion of patients undergoing surgery. The high percentage of emergent operations suggests a weak recognition of spine tumors in children and should prompt a call for increased awareness of this cancer. In spite of these findings, lack of tumor type identification was a limitation to this study.

Dynamic susceptibility contrast and dynamic contrast-enhanced MRI characteristics to distinguish microcystic meningiomas from traditional Grade I meningiomas and high-grade gliomas

OBJECTIVE Microcystic meningioma (MM) is a meningioma variant with a multicystic appearance that may mimic intrinsic primary brain tumors and other nonmeningiomatous tumor types. Dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI techniques provide imaging parameters that can differentiate these tumors according to hemodynamic and permeability characteristics with the potential to aid in preoperative identification of tumor type. METHODS The medical data of 18 patients with a histopathological diagnosis of MM were identified through a retrospective review of procedures performed between 2008 and 2012; DSC imaging data were available for 12 patients and DCE imaging data for 6. A subcohort of 12 patients with Grade I meningiomas (i.e., of meningoepithelial subtype) and 54 patients with Grade IV primary gliomas (i.e., astrocytomas) was also included, and all preoperative imaging sequences were analyzed. Clinical variables including patient sex, age, and surgical blood loss were also included in the analysis. Images were acquired at both 1.5 and 3.0 T. The DSC images were acquired at a temporal resolution of either 1500 msec (3.0 T) or 2000 msec (1.5 T). In all cases, parameters including normalized cerebral blood volume (CBV) and transfer coefficient (kTrans) were calculated with region-of-interest analysis of enhancing tumor volume. The normalized CBV and kTrans data from the patient groups were analyzed with 1-way ANOVA, and post hoc statistical comparisons among groups were conducted with the Bonferroni adjustment. RESULTS Preoperative DSC imaging indicated mean (± SD) normalized CBVs of 5.7 ± 2.2 ml for WHO Grade I meningiomas of the meningoepithelial subtype (n = 12), 4.8 ± 1.8 ml for Grade IV astrocytomas (n = 54), and 12.3 ± 3.8 ml for Grade I meningiomas of the MM subtype (n = 12). The normalized CBV measured within the enhancing portion of the tumor was significantly higher in the MM subtype than in typical meningiomas and Grade IV astrocytomas (p < 0.001 for both). Preoperative DCE imaging indicated mean kTrans values of 0.49 ± 0.20 min-1 in Grade I meningiomas of the meningoepithelial subtype (n = 12), 0.27 ± 0.12 min-1 for Grade IV astrocytomas (n = 54), and 1.35 ± 0.74 min-1 for Grade I meningiomas of the MM subtype (n = 6). The kTrans was significantly higher in the MM variants than in the corresponding nonmicrocystic Grade 1 meningiomas and Grade IV astrocytomas (p < 0.001 for both). Intraoperative blood loss tended to increase with increased normalized CBV (R = 0.45, p = 0.085). CONCLUSIONS An enhancing cystic lesion with a normalized CBV greater than 10.3 ml or a kTrans greater than 0.88 min-1 should prompt radiologists and surgeons to consider the diagnosis of MM rather than traditional Grade I meningioma or high-grade glioma in planning surgical care. Higher normalized CBVs tend to be associated with increased intraoperative blood loss.

Artificial Immune Systems for Identifying Malignant Breast Cancer

Cancer is a gene disruption based disease in which, body’s cells behave abnormally. These cancerous cells start uncontrolled reproduction and usually offend organisms, and a mass of cancerous cells is called tumor. Epidemiological studies have revealed that breast cancer is the leading cause of mortality among female population. Owing to the essence of natural lipid masses in breast, identification of tumor type from mammographic images is challenging. In this sense, almost patients are supposed to have biopsy operation which might lead wide variety of side effects. On this basis, a novel expert system based on negative selection and fuzzy sets is proposed to save assistantship functionality for specialists and physicians. In some sense, multiple pattern repositories are injected into the infrastructure of artificial immune systems. To verify and validate the proposed approach, several computational simulations have been performed. Simulation results prove that proposed method provide more accurate results in identifying malignant tumors in comparison to traditional pattern recognition techniques as such artificial neural networks and neuro-fuzzy systems.

Abstract A75: Translational studies of a first-in-class FASN Inhibitor, TVB-2640, linking preclinical studies to clinical laboratory observations in solid tumor patients

Abstract Dysregulated expression of FASN is a central mediator of neoplastic lipogenesis. FASN catalyzes the production of palmitate, the building block of long chain fatty acids, providing a mechanism to convert glucose and other carbon sources into lipids needed for production of phospholipids, formation of lipid rafts and the subsequent assembly of receptor tyrosine kinases and other signaling molecules in microdomains juxtaposed to the membrane. Inhibition of FASN in tumor cells leads to disruption of PI3K/Akt/mTOR and other important pathways leading to apoptosis. Targeting this critical nexus between lipogenesis and cellular survival/proliferation signaling pathways makes inhibition of FASN a novel therapeutic approach with a strong biological rationale and 3-V Biosciences has initiated clinical studies with its first-in-class FASN inhibitor. 3-V Bio has developed a series of orally available, reversible, potent, and selective FASN inhibitors that remodel tumor cell membranes, disrupt pAkt and Wnt/beta-catenin pathways, and reprogram gene expression. These effects lead to apoptosis of tumor cells in culture, inhibition of anchorage-independent cell growth under lipid-rich conditions and inhibition of in vivo xenograft tumor growth in mice and rats. We are currently using transcriptomic and metabolomic analyses, including lipidmomic profiling, to explore the fundamental mechanisms resulting in sensitivity to the FASN inhibitor, TVB-3166. These same platforms are used to examine the changes in response to FASN inhibition in tumor and surrogate tissues of xenograft models as well as surrogate tissues of cancer patients. A panel of tumor and normal cell lines was assembled and lipids were assessed prior to and 72 hours after treatment with TVB-3166. A reduction of saturated fatty acids was observed in all cell lines indicative of FASN inhibition. A similar extent of reduction was observed in media in the presence of 1% or 10% serum; these results demonstrated that the tumor cells did not compensate for FASN inhibition by increasing uptake of saturated fatty acids from the extracellular milieu. An inverse correlation was observed between the pretreatment quantities of saturated fatty acids and the induction of apoptosis resulting from FASN inhibition with TVB-3166; low levels of saturated fatty acids in cell lines such as COLO-205, correlated with a high level of cell killing. Normal, untransformed cells had significantly higher levels of pretreatment saturated fatty acids and a commensurate insensitivity to TVB-3166. These in vitro observations were extended to a COLO-205 rat xenograft model. Significant tumor growth inhibition was measured in these animals in response to FASN inhibition by TVB-3166. Tumor tissues were isolated and a reduction in pAkt and c-Myc expression were observed, the latter consistent with a reduction of Wnt/beta-catenin driven transcription. Further metabolomic analyses of surrogate and tumor tissues from this model continue. The power of the metabolomic/lipidomic and transcriptomic analyses to evaluate drug responsiveness was applied to surrogate tissues of a small number of cancer patients treated with the FASN inhibitor, TVB-2640. Following 8 days of oral dosing, a preliminary evaluation of aqueous metabolites and lipids in patients' sera demonstrated changes consistent with the mechanism of FASN inhibition. Larger numbers of patients are being evaluated in order better characterize the extent of these changes. Preclinical evaluations of the molecular transformations caused by 3-V Bio's FASN inhibitors are being translated into clinical assessments that may ultimately lead to a more complete understanding of the impact of FASN inhibition in cancer patients and potentially the identification of tumor types that are likely to respond to treatment. Citation Format: Doug Buckley, Tim Heuer, Marie O'Farrell, Bill McCulloch, George Kemble. Translational studies of a first-in-class FASN Inhibitor, TVB-2640, linking preclinical studies to clinical laboratory observations in solid tumor patients. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A75.

Abstract A43: Immunologic profiling of pediatric malignancies for plausible immunotherapeutic trial selection

Abstract Although clinical trials have resulted in significant improvement in the treatment of childhood cancers, further progress using more targeted and less toxic modalities requires a better understanding of the biology of these diseases, including how they develop the ability to overcome rejection by the immune system. In adult cancers, immunotherapies are gaining traction with increasing reports of antitumor efficacy. Cytotoxic T lymphocytes (CTLs) have a major role in the immune response to tumors and require antigenic presentation in the context of Major Histocompatibility Complex (MHC) Class I. Studies have reported the degree of these tumor-infiltrating lymphocytes to be directly correlated with prognosis. Prior studies have also shown that MHC Class I is down-regulated in 40-90% of adult cancer cases, making them resistant to an immune attack by CTLs, and have indicated that MHC Class I expression down-regulation is associated with poorer prognosis. Some immunotherapeutic approaches, such as chimeric antigen receptors and bi-specific antibodies, are MHC Class I-independent. Others, such as vaccines and the adoptive transfer of tumor-specific T-cells, depend upon antigenic peptide presentation by MHC Class I to be effective. In addition to direct oncolysis, oncolytic viruses exert their therapeutic effects in part by inducing a T-cell response against tumor-associated antigens, rendering their benefits to be also somewhat MHC-dependent. Oncolytic herpes simplex virus (oHSV) therapy is an emerging immunotherapeutic platform in clinical trials, and our lab has previously characterized implantable mouse RMS tumor cell lines for their suitability as immunocompetent models for the study of the adaptive immune response to oHSV therapy. For the appropriate enrollment of patients onto immunotherapeutic clinical trials, it is imperative to know the MHC Class I expression on tumor cells, and, for virotherapy, the effects of infection on its expression. We sought to characterize MHC Class I expression in pediatric malignancies and queried mRNA microarray databases including clinical and preclinical datasets. We characterized the immunologic profile of pediatric malignancies through the identification of tumor types which exhibit MHC Class I and the associated β-2-microglobulin molecule expression. Preliminary data suggest that sarcomas, including Ewing sarcoma, osteosarcoma, and both embryonal and alveolar rhabdomyosarcomas (RMS), Wilms' tumors, and some brain tumors, such as atypical teratoid/ rhabdoid tumors (AT/RT) and ependymomas, exhibit decreased MHC Class I mRNA levels relative to other cancer types. We discovered that MHC Class I can be up-regulated in vitro in many human pediatric cancer cell lines, indicating a reversible epigenetic mechanism for down-regulation. Our immunocompetent murine RMS models suggest that the oHSV in vivo therapeutic effect is largely T-cell dependent. The most resistant model exhibited a cellular infiltrate dominated by CD4+ T cells, while the sensitive model demonstrated higher baseline CD8+ T cells. In fact, the best therapeutic response, including complete tumor rejection and resistance to tumor re-challenge, correlated with highest CTL infiltrate and the highest MHC Class I expression. These data support the likelihood that the oHSV therapeutic effect is not necessarily governed by susceptibility or permissiveness to oHSV oncolysis, but rather by the effect of oHSV on tumor cell-microenvironmental immunologic interactions. We hypothesize that MHC Class I status may serve as an important biomarker for patient inclusion in therapeutic trials of MHC-dependent immunotherapies such as oncolytic viral therapy, and modulation of MHC Class I expression will be a promising strategy to enhance immunotherapeutic efficacy. Citation Format: Kellie B. Haworth, Jennifer L. Leddon, Chun-Yu Chen, Timothy P. Cripe. Immunologic profiling of pediatric malignancies for plausible immunotherapeutic trial selection. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A43.

Abnormality Segmentation and Classification of Multi-class Brain Tumor in MR Images Using Fuzzy Logic-Based Hybrid Kernel SVM

Image classification is one of the typical computational applications widely used in the medical field, especially for abnormality detection in magnetic resonance (MR) brain images. Medical image classification is a pattern recognition technique in which different images are categorized into several groups based on some similarity measures. One of the significant applications is the tumor type identification in abnormal MR brain images. The proposed multi-class brain tumor classification system comprises feature extraction and classification. In feature extraction, the attributes of the co-occurrence matrix and the histogram are represented within the feature vector. In this work, the advantage of both co-occurrence matrix and histogram to extract the texture feature from every segment is used for better classification. In classification, the fuzzy logic-based hybrid kernel is designed and applied to train the support vector machine for automatic classification of four different types of brain tumors such as Meningioma, Glioma, Astrocytoma, and Metastases. Based on the experimental results, the proposed brain tumor classification method is more robust than other traditional methods in terms of the evaluation metrics, sensitivity, specificity, and accuracy.

GAD1 is a biomarker for benign and malignant prostatic tissue

Tissue-specific markers are useful for identification of tumour type in advanced cancers of unknown origin. This study investigated the expression of glutamate decarboxylase 1 (GAD1) in prostate and control tissue compared with the established prostate-specific markers prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA). A tissue microarray was constructed of 36 prostate adenocarcinomas, eight benign prostate samples and benign and malignant control tissues from urinary bladder, lung and rectum. Immunohistochemistry for GAD1, PSA and PSMA was performed. The products of staining intensity and extent were analysed. The GAD1 antibody was validated by Western blot. Real-time polymerase chain reaction (RT-PCR) was performed on malignant and benign samples from each tissue type. GAD1 and PSA immunostains were significantly stronger in malignant and benign prostatic tissue than in controls. PSMA was stronger in prostate cancer than in urothelial and rectal cancer but had a lower specificity than GAD1 and PSA. GAD1 expression decreased with increasing Gleason score. RT-PCR confirmed the presence of mRNA for GAD1, PSA and PSMA in prostate samples. GAD1 is expressed in benign and malignant prostatic tissue and may serve as a highly prostate-specific tissue biomarker.

The Protein Farnesyltransferase Regulates HDAC6 Activity in a Microtubule-dependent Manner

The cytoplasmic deacetylase HDAC6 is an important regulator of cellular pathways that include response to stress, protein folding, microtubule stability, and cell migration, thus representing an attractive target for cancer chemotherapy. However, little is known about its upstream regulation. Our previous work has implicated HDAC6 as a new protein target for the farnesyltransferase inhibitors (FTIs), although HDAC6 lacks a farnesylation motif. Here we show that the protein farnesyltransferase (FTase) and HDAC6 are present in a protein complex together with microtubules in vivo and in vitro. FTase binds microtubules directly via its alpha subunit, and this association requires the C terminus of tubulin. Treatment with an FTI removed FTase, but not HDAC6, from the protein complex, suggesting that the active form of FTase is bound to microtubules. Importantly, the removal of FTase from microtubules abrogated HDAC6 activity, as did a stable knockdown of the alpha subunit of FTase (FTalphaKD). Interestingly, the FTalphaKD cells showed increased sensitivity to the antiproliferative effects of Taxol and the FTI lonafarnib when used either as single agents or in combination as compared with parental cells. Altogether, these data suggest that FTase, via its tubulin-association, is a critical upstream regulator of HDAC6 activity and that FTase expression could help stratify cancer patients that would most benefit from this treatment.

Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (124I-cG250) and PET in patients with renal masses: a phase I trial

Preoperative identification of tumour type could have important implications for the choice of treatment for renal cancers. Antibody cG250 reacts against carbonic anhydrase-IX, which is over-expressed in clear-cell renal carcinomas. We aimed to assess whether iodine-124-labelled antibody chimeric G250 ((124)I-cG250) PET predicts clear-cell renal carcinoma, the most common and aggressive renal tumour. 26 patients with renal masses who were scheduled to undergo surgical resection by laparotomy received a single intravenous infusion of 185 MBq/10 mg of (124)I-cG250 over 20 min in this open-label pilot study. Surgery was scheduled 1 week after (124)I-cG250 infusion. PET and CT scanning of the abdomen, including the kidneys, within 3 h before surgery was planned for all patients. The obtained images were graded as positive (defined as a tumour-to-healthy-kidney ratio >3 to 1) or negative for antibody uptake, and the surgeon was informed of the scan results before surgery. After surgery, resected tumours were histopathologically classified as clear-cell renal carcinoma or otherwise. The trial is registered on the clinical trials site of the National Cancer Institute website http://clinicaltrials.gov/ct/show/NCT00199888. One patient received inactive antibody and was excluded from analysis. 15 of 16 clear-cell carcinomas were identified accurately by antibody PET, and all nine non-clear-cell renal masses were negative for the tracer. The sensitivity of (124)I-cG250 PET for clear-cell kidney carcinoma in this trial was 94% (95% CI 70-100%); the negative predictive value was 90% (55-100%), and specificity and positive predictive accuracy were both 100% (66-100% and 78-100%, respectively). PET with (124)I-cG250 can identify accurately clear-cell renal carcinoma; a negative scan is highly predictive of a less aggressive phenotype. Stratification of patients with renal masses by (124)I-cG250 PET can identify aggressive tumours and help decide treatment.

Magnetic Resonance Imaging Features of Feline Intracranial Neoplasia: Retrospective Analysis of 46 Cats

The purpose of this retrospective study was to determine the magnetic resonance imaging (MRI) characteristics of feline brain tumors and to determine whether these characteristics can be used to accurately predict the histologic diagnosis. MRI scans of 46 cats with histologically confirmed brain tumors were reviewed, including 33 meningiomas, 6 lymphomas, 4 gliomas, 2 olfactory neuroblastomas, and 1 pituitary tumor. MRI features including axial origin, shape, location, signal intensity, contrast enhancement, peritumoral edema, and mass effect were reviewed and characterized for each tumor type. Tumor shape, axial origin, contrast enhancement, and degree of peritumoral edema aided in the identification of tumor type. Meningiomas were always extra‐axial and were most often ovoid with marked contrast enhancement and mild peritumoral edema. Gliomas were always intra‐axial with ring enhancement and generally caused more peritumoral edema than other tumors. The brain tumor was detected on MRI in 45 (98%) cats. Two blinded independent reviewers correctly identified 82% of all of the tumor types on the basis of MRI appearance alone. Thus, MRI is an excellent diagnostic tool for the detection of brain tumors in cats, and it provides important information to aid in the diagnosis of tumor type.

Ultrastructural markers in the pathologic diagnosis of pituitary adenomas.

The functional-morphologic classification of pituitary adenomas increased the number of distinguishable morphologic entities from 3 (acidophilic, basophilic, chromophobic) to 15. Identification of tumor types requires histology as well as immunohistochemistry and electron microscopy. Electron microscopy has a pivotal role in the recognition and separation of entities with overlapping immunohistochemical profiles. Electron microscopic diagnosis is facilitated considerably by structural markers present in the majority of adenoma types. Two groups of ultrastructural markers are discussed. Organelle markers are represented by specific morphology/arrangement of ubiquitous cytoplasmic constituents (rough endoplasmic reticulum, Golgi apparatus, mitochondria). Special markers are usually restricted to a particular pituitary cell type, its tumors, or both (filamentous aggregates, particular morphology of secretory granules, etc). Evaluation of general ultrastructural features and identification of structural markers permit conclusive diagnosis in the majority of pituitary adenomas. Cell derivation remains uncertain in many so-called clinically nonfunctioning adenomas with no or insufficient markers and poorly developed cytoplasmic organization associated with low endocrine activity.

Detection of gastrin mRNA in human antral mucosa and digestive endocrine tumors by in situ hybridization: a correlative study with immunocytochemistry and electron microscopy.

In gastrinomas, as well as in other endocrine tumors whose hormone overproduction is responsible for clinical syndromes, antibodies against the bioactive form(s) of hormones can fail to detect immunoreactivity. Moreover, tumor secretory granule morphology may fail to allow tumor type identification. The use of anti-pre-pro-gastrin antibodies has been proposed as an alternative to identify gastrinomas. The aim of the present study was to demonstrate that in situ detection of gastrin mRNA may represent another possibility. A 35S-labeled cDNA probe encoding the human gastrin pre-pro-hormone was used to localize gastrin gene transcripts in antral mucosa and digestive endocrine tumors from patients with a Zollinger-Ellison syndrome characterized by high serum gastrin levels. In situ hybridization was combined with light and electron microscopic immunostaining of the bioactive gastrin 17/34 form and morphological study of secretory granules. Gastrin mRNAs were detected in antral gastrin cells and in a variable proportion of tumor cells in all endocrine tumor studied. Transcript expression correlated well with immunohistochemical staining and granule ultrastructure for most of the tumors, and provided crucial evidence for identifying as gastrinomas two tumors with weak immunoreactivity and poorly granulated cells. Our data show that in situ hybridization is a sensitive method for gastrin mRNA detection and represents a valuable tool for the identification of gastrinomas.

Monoclonal antibodies to intermediate filament proteins. Use in diagnostic surgical pathology.

Surgical pathologists base diagnoses upon characteristic features of neoplasms such as gland formation, papillary structures, and the spindle shape of tumor cells. Tumors without obvious differentiated features pose diagnostic problems because they lack the features that allow an accurate identification of tumor type. In such situations, one depends upon ultrastructural analysis by electron microscopy or relatively nonspecific histochemical stains to gain a clue as to the identity of the neoplasm. Clearly, what has been lacking in diagnostic pathology is a set of well-characterized tissue-specific reagents capable of distinguishing among different cells. Recently, anti-intermediate filament protein antibodies have been employed to distinguish cell type in poorly differentiated neoplasms.

The EMI scanner. A brief review of the first 650 patients.

Abstract The results obtained from the EMI scans of the first 650 patients are reviewed. Disease processes are seen as changes in the capacity of tissues to absorb X-ray photons, often with a demonstration of the distorted anatomy. The method operates most accurately where there is a large difference between the absorption values of diseased tissue and those of normal brain. This large difference in absorption values is best seen in lesions arising from trauma and cerebro-vascular accidents. The distinction between all types of haematoma which have high absorption values and cerebral oedema which has a low absorption value is relatively simple. In cerebro-vascular accidents a distinction between haemorrhage and infarction may be made. Infarction may show as a region of low absorption values as early as eight hours. Tumours produce visible change in a high percentage of cases but identification of tumour type is not often possible. Infarction, infection, coagulative necrosis, oedema and unclotted blood may...