Sunday, February 28, 2010

A Journey into the Unknown

Things did not come easily to him. They did, but not the kind the world expected of him. The arduous task of the mundane schoolwork took hours instead of minutes. Time would fly while he hunted for answers. He would often, in class, imagine the view from ten feet or twenty feet above the classroom, trying to find his compass of reference. The falling leaf outside the classroom window would generate images of the coursing veins arborizing through the green meat of nature. Nature’s chlorophyll at work suddenly bereft of the nutrients as the sap supply constricted by the sting of winter sacrificed a part of self for the preservation of the whole. He had thoughts that flowed and circulated in his mind every waking moment; thoughts that most fifteen-year-olds would not consider, given the constraints of their hormones and the ample supply of the opposite sex playing games of chance.

That day the subject in biology, about the mind, consumed him. What was the mind? There was no form or formal structure or a structural format. It was an arbitrariness of human thought housed within the ethereal container. There was the brain with its well-defined structure. But that was the brain not the mind. He had seen a brain contained within a jar filled with formalin. The deep sulci and the gyri all twisted and contorted to create a larger package of brain cells then would be contained in a smooth round containment. The brain was a brilliant design of more with less. His mind reeled away into a virtual display of electrons firing within the confines of the brain – a concept he had realized in the library about the nature of brain activity. How was a lifetime of information stored to be called a mind. Philosophy aside, did the brain have a mind of its own or was it vice-versa? Questions that were not being discussed by the grey-bearded professor of psychophysiology.

                                       The Brain's Neural Network

“Tom, are you okay?”
“What happened?”
“You had a seizure.”
“Where am I?”
“Hospital.” His mother said holding his hand. He could feel the tense sweat of fear in his mother’s hand.
“I’m okay mom.” She just nodded as a tear escaped the lower lid of her right eye, unable to answer with the piling-on of emotions. Just then a tall man in a white coat walked in.
“Hello Tom. How are you feeling?” He said with his hands cradling the electronic pad.
“Neat, is that an iPad?”
“Why yes. We just outfitted the hospital with it so we have all the information instantaneously updated.”
“Isn’t that dangerous?”
“How so?”
“Well what if the information is incomplete or erroneous?”
“We have people who constantly verify the information. Do you want to look at an image of your brain?”
                                MRI image of the brain (Side view)

Tom’s mother startled, moved in closer to protect her son.
“That’s okay, Toms brain image is perfectly normal.”
Tom looked at the image on the iPad screen. “Neat.” He said and then followed it with “awesome.”
“What we would like is for Tom to undergo a fMRI.”
“What is that?” Tom’s mother inquired.
“It is an MRI that evaluates the function of the brain that an image alone cannot pick up.”

“Any danger with this test?”
“No, none at all.”

                                 Varian MRI 3 Tesla Scanner

Something happened to Tom that day and the large machine housed in the basement of the hospital grunting through its battery of “knocks” would decipher the cause. He realized that he needed to know all about this Rat-at-tat noise-creating machine and all it could decipher.
  CT scan image on top, MRI -left middle, fMRI -right middle, MRI T2 weighted image -below

Our lives exist on simple plains of truth and perceived reality. It is as Nicholai Tesla said “Today's scientists have substituted mathematics for experiments, and they wander off through equation after equation, and eventually build a structure which has no relation to reality.” There are truths that lie dormant ready to be exposed but a narrowed vision keeps them from that discovery.

Understanding nature requires us to allow the overwhelming time and space to imbue our senses and through this whole decipher the many thousands of truths that exist in life.
Several of the greatest minds have accomplished their greatest deeds via this journey.

Arhimedes in his eureka moment said "Give me a place to stand and I will move the earth"

Charles Darwin in his formulation of the Origin of species gave credit to Malthus, "In October 1838, that is, fifteen months after I had begun my systematic inquiry, I happened to read for amusement Malthus on Population, and being well prepared to appreciate the struggle for existence which everywhere goes on from long- continued observation of the habits of animals and plants, it at once struck me that under these circumstances favourable variations would tend to be preserved, and unfavourable ones to be destroyed. The results of this would be the formation of a new species. Here, then I had at last got a theory by which to work".

And Marcel Proust came to his conclusions of memory evocation from his mother’s baking genius, “She (Marcel's mother) sent for one of those squat plump little cakes called "petites madeleines," which look as though they had been molded in the fluted valve of a scallop shell … I raised to my lips a spoonful of the tea in which I had soaked a morsel of the cake. No sooner had the warm liquid mixed with the crumbs touched my palate than a shudder ran through me and I stopped, intent upon the extraordinary thing that was happening to me. An exquisite pleasure invaded my senses …
And suddenly the memory revealed itself. The taste was that of the little piece of madeleine which on Sunday mornings at Combray … when I went to say good morning to her in her bedroom, my aunt Leonie used to give me, dipping it first in her own cup of tea or tisane …. and the whole of Combray and its surroundings, taking shape and solidity, sprang into being, town and garden alike, from my cup of tea.”

Over the next week, Tom read every piece of information he could lay his hands on about MRI machines and their use. The first image was created in 1973 some 27 years ago.. The imaging of the Magnetic Resonance Imaging (MRI), he learned is based on the principles of differential tissue densities. Since human body is mostly water based, different tissues have different densities and thus have different amounts of water levels. Each molecule of water has two hydrogen atoms, each of which have a proton. Each of these protons is in a spin mode, like tops lying on their sides. When a strong magnetic field is created around these protons they become coherent (start spinning) in their spin axis to directionally point to the magnetic field. As the magnetic field is turned on and off the protons have a “loss of phase coherence” which means the tops stop spinning when the giant invisible hand of the magnetic field stops using the force causing them to fall to one side or another (“they no longer precess around an axis along the direction of the magnetic field.”). The rate of initial deflection and the transient difference between different tissues (example the liver and kidney) will lead to a difference in that rate of change and that can be plotted by a computer as an image.

                                 T1 image generation by Enthalpy (1 second)

                                 T2 image generation by Entropy (1/1000 of a second)

Tumors are detected because the protons within the cells return to their equilibrium state at different rates.

The fMRI or functional MRI exploits the rate of blood flow to the parts of the brain that are working hard. 

                            MRI image of Homer Simpson's brain

                          fMRI image of a Homer Simpson's brain

It is called BOLD (Blood-Oxygen-Level Dependent). For instance if one is thinking about a birthday party or a math exam, then certain areas of the brain will get more blood flow then others, similarly if one is reading different parts of the brain will get more blood supply. 

                              Brain anatomy with fMRI image 

                                 fMRI image of the visual fields cortex

The brain cells do not carry a cache of oxygen, they are dependent on the rate of blood flow to extract oxygen. Depending on the neurons (brain cells) that are firing for that thought determines the intensity of the thought and hence the rate of cerebral blood flow.

                      Top: Oxygenated fMRI image, Bottom: deoxygenated fMRI image

 Limited thoughts of low consequence will not be depicted due to the “signal-to-noise ratio” being small. To enhance the signal one has to increase the magnetic field. Interestingly, oxygenated or arterial blood is diamagnetic which can align itself as normal tissues under a powerful magnetic field while the de-oxygenated blood loses that ability (paramagnetic) and this variance can be exploited to create an image with appropriate coloring to indicate active functional areas in the brain. The larger the magnetic field the better the image. Three-quarters of the BOLD signal arises from larger vessels in a 1.5 Tesla MRI scanner, enhancing the scanner to 7 Tesla results in 70% of BOLD signal from the small blood vessels.. Furthermore, the size of the BOLD signal increases roughly as the square of the magnetic field strength.

                        Blood vessel distribution in the brain

                     Photomicrograph of the brain and blood supply (microscopic view)

“Yes Tom. What is it?”
“I want to go to the hospital.”
“What’s wrong?”
“Nothing mom, I want to talk with that doctor.”
“I have some information for him.”
“Tom he is a busy man. We can’t just barge in on him.”
“All I need is one minute of his time.”

The waiting room was empty of patients. The constant but muted speakers overhead came to life periodically to announce different doctors names and which department they needed to call. The austere environment replete with organization of chairs and tables laid the framework of the human-life-saving environment.

“Hi Tom. How are you feeling?”
“Fine. I was looking into the MRI machine and its functions and I had a thought.”
“Aren’t you supposed to be learning basic biology at this stage?”
“Yes, I suppose, but I had a thought. This might sound nuts to you.”
“Go ahead. A brilliant electrician once said, “The scientists of today think deeply instead of clearly. One must be sane to think clearly, but one can think deeply and be quite insane:” He said as he quickly looked at his watch. Time is always in short supply in medicine.

“What if you vary the magnetic fields of each collection of images wouldn’t you get a better super-imposed image at varying relaxation modes of different tissues?”
“Well, Tom, I am not a physicist, but I do know that the equipment comes in selected Magnetic Powers, for example; the first MRI scanner we had was 1.5 Tesla and now we have upgraded it to a 5.7 Tesla which has almost a four fold increase in the magnetic field. But I don’t know if they can vary the power settings. I guess that would be an interesting idea to explore.” He cupped his hand around his chin in thought. “Okay if you read all this then here is a question. What is 1 Tesla equal to?”

“10,000 Gauss.” Tom exclaimed proud of his recent readings.
“Tom you will be a great scientist one day soon.”

“Well, I also read Nicholai Tesla, you quoted him earlier. He was the one who was able to harness the energy in the electrical field in the alternating current. He sold that to the Westinghouse Company.”

“How do you know all that?” The doctor’s eyes were wide with interest and admiration.
“I read it and because of his outlandish behavior he died penniless in a room in New York City.”

                                 Nicholai Tesla (last image) 1856-1943

The doctor came and sat down next to Tom. “You are a smart one.” He turned to Tom’s mother, “Maybe he should be considered for Johns Hopkins, Harvard  or Princeton..”
“Uh huh.” Tom’s mother was speechless.
“So, I just got the results of the fMRI on you Tom and you have a condition called Migraine. It is nothing to worry about. It is very episodic – er…you know what that word means?”

“I thought so. Anyway these episodes are very infrequent and you will have some prodrome or a signal that the seizures are about to occur. Did you have any?”
Tom thought for a moment, “I felt like I was watching the class from above with my brain firing electrical signals.”

“Wow that’s a new one on me. I usually get simpler prodromes. Anyway, then you will know when it occurs and you can protect yourself.” Some people have headaches, others see distorted vision, you know like looking at the wall as it dissolves or it gets pinched from one side or another.”

“Like Dali’s paintings?”

                                             Dali's Painting

“Yes. My you sure know a lot of stuff?
”One more question?”
“Sure, shoot. This is more fun then what I have to do next.”
“How can a MRI tell if you are lying or telling the truth?”
“There are a couple of companies; No lie MRI in California and Cephon in Massachusetts that have developed an algorithm based on trials which have shown a 78 to 94% accuracy.”
“I should get that to make sure that Tom is doing his homework on time.” Tom’s mother piped in.
“I read that they used it for legal methods to convict a person.”
“There was a case, I don’t remember the name but fMRI was used as supporting material. The primary method of conviction however was the DNA fingerprint. We talked about that in our Radiology Conference. Boy you really dig into things.” He patted Tom’s shoulder and said, “Tom it is a pleasure knowing you.”

                           Brian Dugan and his victim Jennie Nicarico

“Thank you sir. Same here.” Tom said and stood up.
“If you need some recommendations let me know, I know some of the University Professors, I can have them evaluate Tom for access to their library and who knows.”
“May I call you again?”

“Sure Tom, I am mostly free on Friday afternoons, call my office if you have a question or thought to discuss, as long as I am not busy with other patients, I will always return your call.”
Sometimes the ready mind that vents to thought, unencumbered with the vicissitudes of life realizes the constructs of understanding better then one that toils at equations and minutiae, grunting and sweating with the unknown only to misuse an equation to fulfill the desire through rationalization.

The multidimensional life that unfolds around us is replete with constraints of certain rules that mankind has devised. These rules fit the understanding of man but it remains unknown whether these rules are what govern the physical processes. Did the Great Mathematician devise the earth and the cosmos based on a few simple rules, or is it that we humans with our limits of understanding are only able to decipher what we see. From the comforts of Newtonian physics to the irritating discomfort and confusion of the Quantum Physics the premise of life is based on thought experiments. Once the thought is expressed, experiments are created to prove that thought. Ours is a life at constant war with the limitations of knowledge. We strive to prove or disprove the intent of our constructs as we try to understand the mind of our Creator. Science like Art is and always will be a journey into the unknown.

The very substance of the ambitious is merely the shadow of a dream

William Shakespeare, Hamlet. Act II

The poet's eye, in a fine frenzy rolling,
Doth glance from heaven to earth,
from earth to heaven,
And as imagination bodies forth
The forms of things unknown, the poet's pen
Turns them to shape, and gives to airy nothing
A local habitation and a name

William Shakespeare, Midsummer Nights Dream V,I

Sunday, February 7, 2010

Musical Interlude - A Frameless Art.

The magnitude of nature’s beauty is wasted on the unflattering eye. It is like a frameless art. Life is a perception of reality. It escapes through the many pores of daily living. The pressures of the survival instincts weigh down on the rituals of enjoyment and happiness; like the sound of a gavel ending the dream-like state of perpetual frivolity. And yet both nature and nurture can survive and we humans can foster an alliance with both. The song of the bird goes heedless on a bright blue day dotted with tiny wisps of clouds. The radiant color of the red rose on a bush remains hidden when the children have to be driven. The smell of jasmine flirts with the olfaction but is relegated in the deep recesses when limits of time are imposed on a daily constitutional.

What is it in humans that function to limit the scope of nature’s treasure? This is a question that pricks the mind and then is laid to rest for other competing arguments.
It was on a fall day when the bluster and blister of the wind kept the crowds huddled within their sweater, overcoats and hats. He waited on the steps of the D.C. Metro Station whiling the time before his train would carry him to his destination of potential lucrative adventure. His eyes wandering over the masses that walked in and out the automatic glass doors. His eyes caught sight of a teenage girl wearing torn jeans, a sweater with sleeves ending well beyond the limits of her outstretched hands and a black knitted ski hat. She sat forlorn in the corner contemplating the vicissitudes of her life or the lost boyfriend or whatever a teenager would think her time away with. On the other wall was a well-dressed thirty-year-old with a briefcase in one hand and a long stem rose in the other. She was also oblivious to the world, carrying the most radiant of smiles as her within poured out of her being. She had found her love and her thoughts revolved around the gift of the rose. An expression of requited love.

A tall stately man wearing a pin-striped suit carrying a briefcase in his right hand his overcoat draped neatly on his left forearm bent at the elbow hesitated a moment, looked at his watch and then with equal and quick dispatch hurried into the hallway towards the departure station of his train ride.

It was then when the lady in the red coat came strolling through her neck held high straining to catch the status of her train time when the first sound of the violin broke through. It started with a gentle sweeping lilting cadence, initially disruptive to the chaotic mass that surrounded it, but then as it built on itself, the melody, pitch and harmony of the solo violin surrounded the square platform. The lady burrowed in her voluminous bag and threw a dollar at the soloist’s feet and hurried on. This was her expression of helping the needy.

The masses still moved at the same pace. Some broke their stride momentarily, while others glanced and yet most appeared to not notice. The music enchanted him. It was the first time he had heard the solo violin being played out in the open. He loved the sound of the violins in a concert. It had a bewitching melodic tug to it, as if it should go on forever and lull him to sleep and awaken him and be around him all times. But this, this was something else. It was the sound of a soloist. He strained his neck over the stairs where he sat and found a young man dressed in a black suit jacket standing erect with the violin perched delicately on his right shoulder held gently by the force of his clean-shaven chin. The crop of his hair partially hidden under a baseball hat dancing madly to the music that emanated from the instrument he held. It was as if the instrument moved him into playing it. The sobbing sorrowed notes merged with the joyous, playful and romantic cadences filling the cramped air of disjointed apathy. The majesty of this spectacle with the ambience and rapturous melody that floated from his instrument was of equal measure. And yet, and yet he was alone with his melody and not a single soul seemed touched. They just hurried to their destination forfeiting this beauty.

The frailty of this quintessence of dust called man lies in self-deception and his intermingled lofty desires. The loss of contentment bleeds from the ruptured vessels of desire. Through this frothy subversion of thought the human spirit continues its “progress” bereft of the melody of life. And to all lives, that come to their natural end the question arises. What was it all about?

A three-year-old clutched and dragged by his mother stopped and yanked his hand away, in defiance to his mother to watch and listen. Something affected him differently then his mother, whose frown and disdain at this impertinence matched the anger that glowered behind her face; they would not be able to catch their ride! The boy persisted in his desire and stood with both his hands clutched together held in between his legs – a melodious defiance, until the mother stepped between the music source and her son’s ears and they moved on.

The janitor on the far side stood with his cleaning tools in his hands enjoying the melody that was not commonplace in this habitat. His head and eyes darting around carefully so as not to get caught shirking his work. The melody of the music lost on him by the rigors of the demands imposed upon him. The tempered feeling that imbued him from this music held his whole while the half-scared, half-defiant selves fought out their battles within.

       Joshua Bell playing at the D.C. Metro Station

A man rested against the wall facing the violinist, he seemed to be enchanted with the melody. Looking once at his watch, he never looked back at it again enjoying the moment. He had musical ears. He remained through most of the 43 minutes of play.
The soloist rested in between pieces for a perfect measure and then resumed the thread of his offering. The teenage girl got up from her corner and walked to the soloist with tears streaming down her unwashed face. She left. The soloist watched her leave but continued to play and there was just the touch of a forlorn whine in the melodic pitch that lasted a few moments in his virtuoso performance.

       Johannes Sebastian Bach's Signature

    Chaconne, Bach's Musical piece for the Violin

He saw all this and wondered at the loss humanity witnesses every minute. But he was going to enjoy it a few minutes longer and take the later train to is destination. He would call his office and announce his delayed arrival. The melody enveloped him. He was one with it. He felt the waves come crashing onto him resisted by his body as they thrashed at him. He felt the rise and fall of the cadence, the change of pitch, the softened notes and those Legato ones that made you crawl within into a place of quiet with a soft blanket, a table lamp and a good book. As if awakened suddenly from this reverie there was a blue sky and a bright sun in his mental enrapture and then all was quiet. No music. He was no longer the king of his infinite space.

The un-repeating melody of Chaconne considered one of the most difficult of all pieces

“Where am I?”
“In the hospital.”
”What happened?”
You were brought in by ambulance from the Metro Station.”
“You are ok now.”
“What was wrong with me?” He said as his hand moved up to his head and he felt the bandage.
“You had a seizure and we discovered a tiny aneurysm inside of the brain that had a contained bleed. You are very lucky.”
I was listening to this man playing the most beautiful music on a violin. The sound was exquisite. I remember…oh!”
“I had an important meeting with my clients.”
“Your wife was here and she took care of that. She told us to tell you not to worry. She will be here in the afternoon.”

Photomicrograph of a dissected Circle of Willis with aneurysm

“Aneurysm?” He repeated mostly to himself. Then he asked if someone would ask his wife to bring his collection of music CDs from his home.
“What is that?”

         Diagram of the A Berry Aneurysm

“It is an out-pouching of the artery in the brain, usually in an area called the Circle of Willis where all the blood vessels branch in and out making a circle. This out-pouching is in the form of a sac with weak walls. It can be genetic or form as a result of atherosclerosis, high blood pressure and other causes. The rising hydrostatic pressure in the artery from high blood pressure can rupture the weak walls and cause stroke.”
He fell silent for a while digesting the information. “How common is it?”

                           The Circle Of Willis

“About 1 in 10,000 people have it.”

“So people are walking around and not knowing it.”
“Unfortunately that is true for a lot of things. But it is more about taking care of yourself with less stress and low blood pressure and contented life that prevents one from being a statistic. However there are a few rare genetically medicated cases where it forms at childhood from collagen vascular development.”

“So what did they do in there.?”

Photograph of the Brain with arrow pointing to the aneurysmal sac in the Circle of Willis

“They clipped the sac.”
“Seems oddly simple.” He mused.
“Since you are doing so well, you can call your wife from your bedside phone.”

That afternoon as the music played from his CD Player, it covered him with a sense of comfort like a soft blanket, one from his past that he had until he was 10 years old. He had to give up the tattered 2 by 4 feet of cashmere blanket because it became a brunt of many jokes from his family and friends. He had traded music for his blanket. Now it seems to bring in the same comfort. Even though the music from this modern equipment was good it did not translate as well, as full bodied, as deep as the one he had heard at the Metro Station. The richness of sound seemed to have been amplified in the confines of those moving hurried masses, the opening and closing doors and the conversations of the rush-hour traffic. There was a one-to-one experience. A richness in the knowledge that the music was for him and only him and yet it also was for others if they chose. That was a sound for a lifetime. It was a memory he would cherish.

That was also the sound that saved his life. Had he been in the train the medical help would have been delayed. Had he been at the high-powered meeting later that morning the aneurysm could have burst and killed him instantaneously. There were so many ifs, that no one could answer. But through it all, it was still the music. To have enjoyed that moment that had saved his life was a gift he would cherish. The sound of that soloist melody etched in his mind once again seized his being and reached his inner sanctum, his eyes closed propelling him into deep sleep. All would be well again. He had his music.

                    Antonio Stradivari 

The soloist at the Metro Station was a world-renowned violinist conducting an experiment to determine the value of value. He had played to huge crowds commanding $1000 a minute and to the Library of Congress and on that day he performed on a 3.5 million dollar 1713 Stradivarius Violin 
                               A Stradivarius Violin

to the lost masses, one of the most intense and brilliant musical notes of all time; Johannes Sebastian Bach’s “Chaconne”.

The mind that sees the frame for the art is blinded to beauty.

If music be the food of love, play on,
Give me excess of it; that surfeiting,
The appetite may sicken, and so die.
Twelfth Night 1,1.