If a structure is interrogated by a given force it will react or respond to the force in a very specific and consistent way.  This is its character . AD

The Common Vein copyright 2009

“For every action there is an equal and opposite reaction.”  Newton’s third Law

Character, nature, or behaviors are grouped in the same category called “character” for the purpose of simplicity.   Character is the most difficult yet usually the most interesting and revealing of all the foundation principles of structure.  How is it defined?  What is done to establish the character of a structure? Why is an elastic band elastic?  Why is rubber rubber?  Why is the nature of the liver described as being like jello?  How is it established that a person has a nature that is short tempered, impatient calm, cruel, bland or dynamic?  How do we establish the character of an abdominal mass and how do we characterize an odd structure like the spleen?  How is it established whether a society is cruel or kind? What does it mean if an organism is gram positive, and what does it mean that the rectal examination is Guiac negative?

What is the common theme of these questions and how do we go about answering them under one umbrella principle?

The best way to conceptualize and define “character” is to think of it as a characteristic reproducible response or reaction to an interrogating force (action reaction).

If an elastic band is provoked by pulling the two ends apart and then it is let go, it will react by snapping back to its former length revealing its elastic nature.  The interrogating force is a pulling force and the reaction is to return to its former length.  Every time the force of pulling is exerted, there is a consistent and predictable reaction.  If any structure performs in this manner, then the adjective “elastic” can be assigned as the property or character of the structure.

In the clinical realm one of the ways the character of a structure is assessed is by palpation.  The interrogating or provoking action is the application of pressure, a gentle push or gentle pull.  A liver may be hard, a mass soft or pulsatile, and skin may lose its elastic tone.  Abdominal palpation is often the key to diagnosing pain.  An inflamed peritoneal cavity is diagnosed by a slow persistent pressure at the site of the pain, followed by a rapid release of the pressure. If the patient’s reacts with a sudden and severe pain that literally makes him/her jump (sounds a little cruel), then this nature indicates peritonism.  Once diagnosed, peritoneal pain takes on a serious and often a surgical direction.  If a patient presents with right upper quadrant pain, and cholecystitis is suspected, constant pressure in the right midclavicular line, below the ninth rib, on a deep inspiration may elicit pain as the gallbladder pushes toward and into the examining hand.  This is Murphy’s sign, and characterizes the disease as acute cholecystitis.

The color of a structure is also a reflection of its character. By definition, when light falls on an object as an interrogating force it will be reflected absorbed or transmitted. As a result its color will be reflected.  Newton observed that light interacts with objects, and some light waves are absorbed, some reflected, refracted, scattered or diffracted.  When light falls on (interrogates or reacts with) a red apple, the skin reflects the red waves and absorbs all the other light waves and so the color red is seen. When the eye sees red the tongue anticipates sweetness; green skinned apples (except golden delicious are generally tart.  When the light waves interrogate the whites of the eyes of a normal patient, all the colors are reflected, the sclera are considered normal in color.  In the jaundiced patient, excess bilirubin causes the yellow or orange spectrum of light to be reflected, and a diagnosis of jaundice is inferred.  Thus the color of a structure is a reflection of its nature and is a way we judge its health.  If the color is pale or has lost its sheen, then added characterization of the tissue allows us to pass judgment on its state of health or disease.

Tools have been developed to help evaluate the character of structure.  The stethoscope, the rubber hammer, and the tuning fork are tools of the early days, carried religiously in the doctor’s bag, and still remain important for bedside examination.  The discovery of the microscope and its use in the study of cells and tissues was a significant advance that opened the biological world of the cell and allowed us to evaluate the size, shape, and position as well as the character of tissue.

Imaging

Diagnostic imaging technologies, starting with the discovery of X-rays by Wilhelm Roentgen in 1895, blossomed in the 20th century.  Through images we gained insight into the macroscopic structure of the body.  Early into the 21st century we are advancing into the structural evaluation of macromolecules and even smaller components.  No matter what is discovered, the principles of structure outlined will remain, and characterization will be one of the most challenging.

X-rays are able to penetrate the body, and they react with tissues and organs in a characteristic manner.  Similar to the interaction of light with surface objects, X-rays react with deep tissues and are either absorbed, reflected, or transmitted.   Air in the body allows the X-rays to go right through and the result is for air to appear black on the X-ray screen.  Soft tissue allows some X-rays through and reflects others, so the tissues have a gray color on the film.  Bone or barium mostly blocks the X-rays and so the structures appear white.  Not only does this technique allow inner structures to be identified, it also allows analysis of their parts, size, shape, and position.  Most importantly, X-ray technology marked the beginning of non invasive characterization of tissue.

CT scanning technology advances the technique by adding interrogative X-rays from multiple angles around the body.  This technique, combined with an ever evolving computer technology, has taken the non invasive evaluation of macroscopic structure to greater heights.   The result has been a significantly widened grayscale, an ability to assign units of density, called Hounsfield units, and an ability to reformat structures in any desired plane.  The latter enabled the first practical objective means of characterizing tissues in clinical radiology.  If a 5cm renal tumor has a 3mm component with a density of -30Hounsfield units, the presence of a small amount of fat in the tumor is confirmed.  A benign tumor called an angiomyolipoma is diagnosed.  In this circumstance the tumor is left alone, and surgery is avoided  Prior to the era of CT technology this mass would have required surgical removal of the whole kidney.

Ultrasound technology interrogates body structures with high frequency sound waves which are reflected, absorbed or transmitted.  This action and interaction enables characterization of tissue in much the same way described by the interaction of  light waves on the surface structures, and X-rays on the deep structures.  MRI technology is slightly different since it uses a strong magnetic field to align the protons of the body, (60-70% of body content), and then adds a brief radiofrequency pulse that changes the alignment of the protons (usually 90 degrees).  The protons are then allowed to relax back to their baseline position within the magnetic field.  The time it takes the protons to relax, is defined as the character of the tissue being imaged.  Thus the protons within the matrix of the liver will have a normal and predictable pattern, and the spleen will have its characteristic but different pattern.  If a malignant squatter invades the liver or the spleen, its pattern or character will be different.  It is this difference that allows recognition.

There are many different MRI sequences which are each designed to emphasize tissue features or characteristics.  For example, T2 weighted images are sensitive to the presence of water.  A cyst in the liver or kidney, normal cerebrospinal fluid and the fluid filled gallbladder will all be bright on T2 imaging. Diffusion weighted sequences are sensitive to Brownian motion of extracellular water, or the lack of it.  These are extremely helpful in the diagnosis of acute infarction of the brain.  The technology can reflect the presence of acute hemorrhage, and can date the bleed by differentiating between deoxyhemoglobin in intact red cells, (0-2days), the change to methemoglobin, (2-14days), and then the change to hemosiderin laden macrophages in the chronic stage (14days to months).  The most useful and most unique advances provided by MRI technology have been its non invasive ability to characterize tissue.

Pathology 

In order for the histologist or pathologist to characterize tissue and cells, he/she employs chemical stains.  These represent a chemical interrogation of the cells.  The hematoxylin and eosin stain (aka H&E) is one of the most widely used stains in histology and histopathology departments.  It involves applying a basic stain called hematoxylin that will color basophilic structures like the nucleus, blue.  The cytoplasm stains pink, as do extracellular and intracellular proteins. In cancer, the blue nucleus is even bluer of the aberrancy of the nucleic acids.  This characteristic is called hyperchromatic by pathologists, and is one of the characteristic features of cancer.  Little crabs are not seen.  Instead the essence of the disease is in the chromatin. This is where the beginning of understanding the disease and potential treatments are being targeted. Non pathologists who have no clue to what they are seeing under the microscope, when seeing too much blue refer to an inside joke of “blueness is badness”.  This of course is in reference to the hyperchromicity of cancer.

Chromosome banding is the technique used to characterize chromosomes.  Quinacrine, a fluorescent dye is used in a technique called Q banding.  After digesting chromosomes with trypsin, Giemsa stain is used in the G banding technique, and the stain is also used after the chromosomes are treated with acid and base and it binds to the centromeres of the cell.  This is called C banding (centromeric heterochromatin banding).    Each chromosome has a unique normal banding pattern that can be viewed and evaluated just like the bar code on a box of Wheaties.

Nanorobotics is a fascinating hypothetical extension of nanotechnology that utilizes both nanotechnology and robotics to interrogate and evaluate the body and its tissues.  Its intended purpose is identification of specific tissues (histonavigation ) by characterization using the speed of sound through the tissues, spectral transmission of optical wavelengths, cell membrane electrical conductivity, characteristic chemical signatures, and surface antigens (Freitas).

The fields of MRI, immunostaining and nanotechnology are cutting edge and wide open for advances, but the principles of characterization remain true, whether via simple palpation or with a nanorobot racing around on a red cell interrogating the tissues.  Characterization captures a reproducible response or reaction to an interrogating force.

 

Principles

Air

 

 

Calcium

When Calcium Means Bad Things

Water

Water density

Fat

Fat density

Soft Tissue

Normal – 4 months Prior and Folllowing Cardiopulmonary Arrest Loss of Gray White Differentiation

70134c01 hx 52 F post cardiac arrest brain cerebrum gray matter white matter gray white differentiation gray white distinction sulci gyri loss of gray white differentiation hypodense dx anoxic injury with diffuse global cerebral edema Davidoff MD Loss of consciousness occurs within 10-15 seconds of cardio-pulmonary arrest. Irreversible brain damage can occur within 5 minutes. gray matter of the brain, particularly the frontal lobes have highest metabolic needsThe occipital, parietal, and temporal lobes and basal ganglia and cerebellum are lower. brainstem lowest needs

Soft tissue density

Blood

Acute Blood

46098c01.800 brain frontal lobe fx hyperintense focus diffusion images fx hyperintense T2 weighted STIR fx dark GRE fx dark T1 dx hemorrhagic infarction hemorrhage acute bleed dx acute hemorrhagic emboli MRI Courtesy Ashley Davidoff

Wegener’s Granulomatois Acute Hemorrhage

47711c01 20 year old male presents with hemoptysis and renal failure chest lungs upper lobes lower lobes infiltrates acinar infiltrates fluffy infiltrates almost symmetrical fx bilateral pulmonary infiltrates renal biopsy dx Wegener’s granulomatosis with pulmonary hemorrhage blood character CTscan Daviddoff MD 47711c02

Wegener’s Granulomatois Acute Hemorrhage Rapid Clearing

47711c02 20 year old male presents with hemoptysis and renal failure chest lungs upper lobes lower lobes infiltrates acinar infiltrates fluffy infiltrates almost symmetrical fx bilateral pulmonary infiltrates renal biopsy dx Wegener’s granulomatosis with pulmonary hemorrhage blood character CTscan Daviddoff MD 47711c01

Elastic Nature

Elastic Artery

47678b04.800 artery aorta histology character normal endothelium media adventitia tunica elastica tunica muscularis

Systole and Diastole in the Elastic Aorta

This image of the theoretical functioning of the role of resistance and outflow enabling the infrarenal aorta to function as second pump. In systole (b) the suprarenal artery is expanded by the pulse but is relatively decompressed by the the low resistance and high flow renal arteries. The infrarenal aorta is relatively more expanded in systole (b) since the iliac arteries offer a relative resistance. This increased resistance causes the elastic tissue in the aorta to stretch (b) so that the recoil in diastole (c) results in a sustained forward moving force assisting the blood to get to their most distal destination – the feet. Courtesy Ashley Davidoff MD. 24877c

Loss of Elasticity

49609c03 abdomen health disease young old time cycle elastic elasticity order disorder Davidoff MD 49609c02

Yielding to Pressure

47753 24 week pregnancy ovary OB fetus amniotic sac placenta bladder fx large left ovarian cyst compressed by pregnancy pressure character water T2 bright MRI scan Davidoff MD concepts

Mobility

Mobile Stone

46462c01s gallbladder moderaste size shadowing mobile stones cholelithiasis USscan ultrasound Courtesy Ashley Davidoff MD copyright 2008

Character and Time

Contrast Enhancement Patterns

Contrast

Enhancing Spiculated Malignant Mass

The finding on this contrast enhanced MRI is a mass in the left breast that is hypervascular and has a spiculated border.  The pathology on this case was an invasive intraductal carcinoma.  Courtesy Priscilla Slanetz MD MPH   42982

Small arterial fed liver lesion

48369c03 40 male with hepatitis B liver fx hypervascular lesion seen in early arterial phase only with rapid wasout dx HCC hepatoma hepatocellular carcinoma capillary hemangioma characterisation characterization blood flow CTscan MRI Courtesy Ashley DAvidoff MD

Liver Lesion s/p RFA

46573 liver fx mass with avascular central region and enhancing rim space occupying disease dx liver metastases metastases dx adrenal mestastasis dx primary lung carcinoma post radiofrequency ablation RFA of large liver lesion CTscan Davidoff MD

Lack of Doppler Flow – Death

46592c01 uterus OB pregnancy fetal demise spontaneous abortion shape size position heart rate USscan Davidoff MD death

Benign Characteristics

Benign Disease

Fig. 1                                                                      Fig. 2 Smooth Margins Well Circumscribed Benign Mass

A mammogram on the left shows an ovoid mass which is hypoechoic with smooth margins.  These findings are characteristic of a benign lesion and could represent a cyst or fibroadenoma as the most likely causes.  The US on the right shows a well circumscribed solid mass characteristic of an adenoma.  Courtesy Priscilla Slanetz MD MPH 42913 42914

Popcorn Shape

This mammogram shows large popcorn shaped calcifications in the left breast characteristic of an involuting fibroadenoma. 42748 Courtesy Priscilla Slanetz MD MPH

Malignant Characteristics

Malignant Characteristics

Shape

Stellate

69595b05.800 star stellate corona radiata spiculated aggressive cancer carcinoma Davidoff art

Davidoff photography

Spiculated Lung Nodule

46361b01 lung fx spiculated nodule dx carcinoma CTscan Courtesy Ashley Davidoff MD

Spiculated Mass in the Right  Breast

This is an MRI of the right breast of a 78 year old patient with a remote history of invasive lobular carcinoma.  The finding on the MRI is characterized by an enhancing spiculated mass.  Recurrent carcinoma was present at pathology. Courtesy Priscilla Slanetz MD MPH 42977

Aggressive Growth

Aggressive Mass Invading the Chest Wall

The CT reveals an obviously aggressive lesion in the left breast of a 66year old female.   It is extending as an irregular mass invading the chest wall posteriorly and projecting through the skin anteriorly.  Courtesy Ashley Davidoff MD 43615

Complexity

Relationship to Gravity

Gallbladder Polyp surrounded by fluid – 3mms

47017c01 gallbladder fx nodule fx adeherent fx non dependant size character through transmission dx gallbladder polyp Davidoff MD

Hard and Soft

Compression and Treatment – Soft to HArd

47187c02.800 back spine lumbar spine L5 compression fracture vertebraplasty MRI Davidoff MD Dr Ram Chavalli

Elastic

Young and Aging Normal Elasticity and Aging Elasticity

49609c03 abdomen health disease young old time cycle elastic elasticity order disorder Davidoff MD 49609c02

Normal aorta and Abdominal Aneurysm – Pressure Tension and Laplace’s Law

70027c01 aorta abdomen abdominal aortic aneurysm normal aorta TCV applied biology AAA USscan Davidoff MD

Pressure Tension Radius Laplace’s Law

This image shows a famous cardiologist, Dr Jonathan Fisher performing as Zippy the clown revealing and exaggerating the difficulty with surface tension and radius in the early stages of blowing up a balloon. Courtesy Ashley Davidoff MD. 60730b01 code lung physiology balloon surface tension surfactant alveolus alveoli radius principles

Infarction

Normal and Global Ischemia after Cardiac Arrest

The two images represent a diffusion weighted MRI image which measures Brownian motion of molecules.  In acute infarction there is restricted Bronian motion of the affected area and the image can be manipulated to present this a s a bright region.  In this case the acute infarction or ischemia (b) is relatively bright compared to the white namatter and compared to the gray matterof the normal (a) 49433c02.800 brain cerebral cerebrum white matter gray matter basal ganglia fx increase intensity in gray matter relative decrease in intensity in white matter dx global ischemia question brain death probable irreversible brain death cerebral infarction s/p arrest MRI DWI diffusion weighted imaging normal and abnormal Courtesy Ashley Davidoff MD

Weak to Strong – Soft to Hard

49586c01 bone thoracic spine compression fracture trauma cement reenforcement wek link units to unity units to dysunity joints treatment CTscan Davidoff MD

Character Change With Treatment

Chemotherapy – Before and 6 weeks After – Metastatic Small Cell Lung Carcinoma

70248c01 liver metastattic small lung carcinoma with diffuse metatstattic disease to the liver )hepatic metastases metastasis before and after treatment 6weeks post chemotherapy successful result size change character change CTscan Davidoff MD 5star